Mesenchymal stem cells and exosomes: A novel therapeutic approach for aging

Highlights
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The hallmarks of aging are diverse and the features interact with each other rather than being independent of each other. This article wants to use hallmarks of aging as an entry point to explore whether improving the relevant indicators can delay aging.
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Mesenchymal stem cells have strong tissue regeneration and repair ability, and exosomes have a number of biological roles, we expect they can also play a role in the delay of aging.
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Currently, exosomes derived from mesenchymal stem cells have been reported in slowing down aging-related diseases, and most of them can be improved by improving aging hallmarks to ameliorate aging-related diseases and slowing down the aging.
Abstract
Mesenchymal stem cells (MSCs), a vital component of the adult stem cell repertoire, are distinguished by their dual capacity for self-renewal and multilineage differentiation. The therapeutic effects of MSCs are primarily mediated through mechanisms such as homing, paracrine signaling, and cellular differentiation. Exosomes (Exos), a type of extracellular vesicles (EVs) secreted by MSCs via the paracrine pathway, play a pivotal role in conveying the biological functions of MSCs. Accumulating evidence from extensive research underscores the remarkable anti-aging potential of both MSCs and their Exos. This review comprehensively explores the impact of MSCs and their Exos on key hallmarks of aging, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, impaired macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Furthermore, this paper highlights emerging strategies and novel approaches for modulating the aging process, offering insights into potential therapeutic interventions.
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Keywords
Mesenchymal stem cellsExosomesAging
1. Introduction
MSCs, a fundamental component of the stem cell family, originate during the early developmental stages from the mesoderm and ectoderm. As adult stem cells, MSCs exhibit remarkable self-renewal capabilities and the potential for multilineage differentiation. These non-terminally differentiated cells display unique properties that encompass features of mesenchymal, endothelial, and epithelial cells. The therapeutic effects of MSCs are primarily mediated through three key mechanisms: cellular differentiation, paracrine signaling, and homing (Uder et al., 2018). However, current scientific consensus highlights paracrine signaling as one of the most critical mechanisms through which MSCs exert their therapeutic effects. MSC-derived Exos, small EVs released via paracrine secretion, are lipid-bilayer-enclosed structures with a diameter ranging from 30 to 100 nm. These Exos encapsulate a wide variety of bioactive molecules, including proteins, mRNAs, and microRNAs, which collectively mediate their functional roles (Spees et al., 2016). Upon secretion, exos can be detected in various bodily fluids including blood, saliva, urine, and breast milk, and subsequently disseminate through the circulatory system to exert regulatory effects on distant cells and tissues (Isaac et al., 2021). MSCs and their Exos have been found to possess a diverse array of functions (Hade et al., 2021; Fraile et al., 2022). Numerous studies have reported their potential involvement in mitigating alterations associated with the fundamental characteristics of aging.
Aging is a physiological phenomenon characterized by the gradual deterioration or decline of various functions in organisms over time, ultimately culminating in death (Shetty et al., 2018). The process of aging is associated with an increased susceptibility and premature onset of numerous diseases, thereby posing a significant risk to human health (Hou et al., 2019). The hallmarks of aging, as reported, encompass genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks pose a significant challenge to understand the mechanisms of aging and achieving delayed aging. Currently, numerous researchers have introduced a range of drugs targeting aging. However, further investigation is required to determine their clinical applicability (Partridge et al., 2020). In contrast, MSCs and their Exos have gained substantial recognition as a safe and effective therapeutic strategy. This comprehensive review seeks to explore the intricate roles and mechanistic contributions of MSCs and Exos in the fundamental biological processes associated with aging.
2. Overview of the biological mechanisms of aging
Aging is an inevitable biological process characterized by a decline in physiological function, including diminished sexual vitality. It is projected that by 2030, individuals aged 60 years or older will constitute one-sixth of the global population, leading to a rise in age-related health challenges (Lavretsky, 2023). The aging process is governed by a set of hallmarks that meet three key criteria: their association with age-related physiological decline, their ability to accelerate aging when experimentally exacerbated, and the potential to mitigate, halt, or even reverse aging through targeted therapeutic interventions (Khaltourina et al., 2020).
The mechanisms driving the progressive decline in functional capacities during aging remain incompletely understood. As a result, the concept of “aging” has been subject to diverse and often conflicting interpretations within the scientific community, and the factors influencing the aging process continue to be a source of ongoing debate (Schmeer et al., 2019). Nevertheless, López-Otín et al. have offered significant contributions by identifying several key hallmarks of aging, including genomic instability, telomere attrition, epigenetic modifications, loss of proteostasis, impaired macroautophagy, and other related elements. Furthermore, aging is characterized by additional challenges such as deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, disrupted intercellular communication, chronic inflammation, and dysbiosis.(López-Otín et al., 2023). It is crucial to note that these indicators do not exist in isolation but rather exhibit interdependence and play a significant role in the aging-related research.
Several pharmacological agents have been developed to target the aging process, with some widely utilized as senoprotective interventions in animal models. A range of drugs, including rapamycin, acarbose, nordihydroguaiaretic acid, estradiol, aspirin, and metformin, have consistently demonstrated effectiveness in extending the lifespan of mice across diverse genetic backgrounds (Nadon et al., 2017; Campisi et al., 2019; Martin-Montalvo et al., 2013; Brosh, 2013). However, further research is required to validate their anti-aging efficacy in animal models. Cell therapy has emerged as a safe and effective strategy in the field of anti-aging treatment. Its fundamental mechanism of action, which targets the root causes of aging, offers long-term benefits with minimal side effects and improved safety over extended use. As a result, it is widely endorsed and provides valuable insights and perspectives for various anti-aging applications.
3. Biological features of mesenchymal stem cells and exosomes
3.1. Biological features of mesenchymal stem cells
MSCs, derived from the mesoderm, are pluripotent stem cells endowed with the capacity for multidirectional differentiation, immunomodulatory properties, and self-renewal. They are widely available from diverse tissue sources (Wang et al., 2023). Notably, MSCs lack major histocompatibility complex II (MHC II) expression and exhibit low levels of costimulatory factors such as CD80, CD86, and CD40, resulting in low immunogenicity—a significant advantage for MSC-based therapies. MSC therapy holds immense potential for treating a broad spectrum of diseases and conditions, as it aims to harness transplanted MSCs to replace or repair damaged cells, tissues, or organs. While significant progress has been made in leveraging MSCs to slow aging, the field continues to face numerous challenges that require further exploration and resolution.
MSCs can contribute to slowing down aging through multiple mechanisms. On one hand, MSC transplantation can exert anti-aging effects via stem cell differentiation. For instance, intervertebral disc degenerative changes (IDD), which are closely associated with aging, can be mitigated by reducing senescent cells, thereby lowering levels of MMP13—a factor that promotes disc degeneration during aging (P et al., 2019). Human umbilical cord MSCs (HUCMSCs) have been shown to differentiate into nucleus pulposus cells (NPCs), replenishing NPC populations and enhancing the synthesis of extracellular matrix (ECM) by NPCs (Huang et al., 2023). However, the differentiation efficiency of MSCs is difficult to control within the complex in vivo environment. To address this, pre-differentiating MSCs into specific cell types prior to transplantation has been proposed to enhance lineage-specific differentiation. Nevertheless, this approach may limit the functional versatility of stem cells post-transplantation. Additionally, MSCs can exert anti-aging effects by stimulating endogenous tissue or cell regeneration. For example, bone marrow mesenchymal stem cells (BMSCs) transplanted into patients with acute myocardial infarction or chronic myocardial ischemia have been shown to remodel the extracellular matrix, promote neovascularization, and recruit endogenous stem cells (Siu et al., 2010). This mechanism highlights another potential strategy for stem cell transplantation in the context of aging.
On the other hand, the paracrine pathway of MSCs also plays a pivotal role in stem cell therapy. For instance, functional mitochondrial transfer from BMSCs has been demonstrated to mitigate Dox-induced cardiomyopathy, as shown in Zhang et al. (Y et al., 2016). Additionally, MSCs secrete a variety of bioactive factors. For example, MSCs produce transforming growth factor-beta (TGF-β) in response to IL-4 receptor-mediated activation of the STAT6 pathway. This process inhibits the proliferation of CD4+ and CD8+ T cells and the secretion of T-helper 1 (Th1) cytokines, while promoting the expansion of regulatory T cells (Treg). Another key factor secreted by MSCs is interleukin-10 (IL-10), an anti-inflammatory and immunomodulatory cytokine also expressed by various immune cells. The expression of IL-10 by MSCs requires direct interaction with T cells (Schulman et al., 2018). Moreover, MSCs exert their therapeutic effects through the release of Exos. Studies have shown that MSC-derived Exos reduce the secretion of pro-inflammatory cytokines (IL-1ß, TNF-α) and enhance the production of TGF-β by peripheral blood mononuclear cells (PBMCs) without affecting PBMC proliferation (Chen et al., 2016). These findings suggest that MSC-derived Exos may serve as a promising alternative to direct MSCs therapy (Fig. 1).
Fig. 1
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Fig. 1. Role of MSCs in anti-aging. MSCs function primarily through their secreted Exos. Exos first form mature exos in the MSCs through multiple stages, then are secreted from the MSCs through cytosis and cytotoxicity, and exert their effects on the recipient cells.

3.2. Biological features of exosomes
The production of exosomes (exos) is a complex process involving multiple stages, including the formation of early endosomes, maturation into late endosomes, and eventual development into functional small membrane vesicles. Initially regarded as cellular byproducts with limited biological significance, exos are now understood to play a critical role in intercellular communication, intracellular signaling, and immune regulation, as evidenced by recent studies (H Rashed et al., 2017; Yin et al., 2022). Exos exhibit dual functionality: they act as key mediators of intercellular communication through mechanisms such as antigen presentation, while also facilitating the removal of harmful molecules from cells or tissues, thereby enabling the identification of potential biomarkers (He et al., 2018). By virtue of these two roles, EVs assume significant role in stem cell therapy (Hu et al., 2022), immunomodulation (Anel et al., 2019), tumor metastasis (Luo et al., 2023), organogenesis (Asmussen et al., 2019), and normal development (Demonbreun and McNally, 2017).
Exosomes (Exos) derived from MSCs have been shown to overcome several limitations associated with stem cell therapy while preserving their fundamental biological properties. Extensive research has demonstrated that the direct intravenous administration of Evs can serve as a viable alternative to stem cell transplantation (Mianehsaz et al., 2019; Psaraki et al., 2022).This approach not only exhibits a pronounced inhibitory effect on tumor growth (Wang et al., 2020), but also effectively retards the aging process in organisms (Lin et al., 2019; Maqsood et al., 2020; Liu et al., 2021; Ahmadi and Rezaie, 2021). Furthermore, it addresses the safety concerns associated with current cell transplantation methods.
MSC-Exos are known to contain a variety of microRNAs (miRNAs) associated with the aging process. Studies have shown that the expression of these miRNAs decreases with aging, leading to a reduction in the differentiation capacity of senescent MSCs and a disruption in the expression of secretory factors. Hisamatsu et al.(Hisamatsu et al., 2016) identified the downregulation of miR-17 and its paralogs, miR-106a and miR-106b (collectively referred to as miR-17/106), as a key factor contributing to the diminished differentiation potential and dysregulated secretory factor expression in senescent MSCs. Further research has corroborated the link between miR-17/106 and the age-related decline in the bone-forming ability of MSCs. For instance, transgenic mice overexpressing miR-17 exhibited enhanced bone tissue development and an extended lifespan (Du et al., 2014) highlighting the critical role of miR-17/106 in maintaining MSCs functionality and combating age-related degeneration.
4. Anti-aging effects of mesenchymal stem cells and exosomes
MSCs play a pivotal role in the aging process. As time progresses, the quantity and functionality of cells within the body decline, contributing to the overall aging of the organism. However, MSCs possess the unique ability to self-renew and differentiate into a diverse array of cell types, thereby supporting the regeneration and repair of bodily tissues. This regenerative capacity positions MSCs as a crucial element in mitigating the effects of aging and promoting tissue homeostasis (Table 1).
Table 1. Anti-aging effects of mesenchymal stem cells and exosomes.

Species Cellular type Hallmarks of aging Function and mechanism Disease Reference
Mouse BMSCs Genomic instability Related to Ercc1, a key enzyme in DNA repair Aging (Dorronsoro et al., 2021)
Monkey BMSCs- EVs reduced DNA damage to oligodendrocytes Cortical damage in the aging brain (Go et al., 2021)
Rat BMSCs Telomere attrition activation of the Notch-1/Jagged-1 signaling pathway Geriatric cardiomyopathy (Chen et al., 2018)
Human ADMSCs MP upregulate the expression of TERT Idiopathic Pulmonary Fibrosis in the elderly (Merino et al., 2021)
Human UCMSCs Epigenetic alterations Decrease in the levels of collagen II and aggrecan Senile diabetes (Qi et al., 2019)
Rat BMSCs-Exos Modulation of connective CTGF by miR-133b reduces tubular EMT and renal interstitial fibrosis. Renal Failure in the elderly (Cao et al., 2021)
Mouse BMSCs-Exos Activation of SIRT1 (sirtuin 1) by miR-29b-3p Insulin resistance in the elderly (Su et al., 2019)
Human UCMSCs Loss of proteostasis Activation of the cMet-AKT-GSK3 signaling pathway with simultaneous down-regulation of hyperphosphorylated tau Alzheimer’s disease (Jia et al., 2020a)
Human BMSCs CD73/ecto-5′-nucleotidase Osteoarthritis (Zhang et al., 2018)
Human OM-MSCs-Exos Alleviated ER stress, and reduced neuronal apoptosis Alzheimer’s disease (Hu et al., 2025)
Human BMSCs Disabled macroautophagy Regulation of the Sirt1/AMPK signaling pathway by miR-199a-5p Idiopathic pulmonary fibrosis in the elderly (Shi et al., 2021)
Human UCMSCs- EVs DDX5 and its interaction with E2F1 were found to facilitate nuclear translocation of DDX5, thereby activating the expression of Atg4B Aged liver regeneration (Zhang et al., 2023)
Mouse BMSCs Bmi1 can reduce oxidative stress and deactivate the p16/p19 signaling pathway Osteoporosis (Chen et al., 2018)
Human UCMSCs Upregulating Beclin-1 Parkinson’s disease (Heris et al., 2022)
Mouse ADMSCs Mitochondrial dysfunction Enhance mitochondrial autophagy, leading to the elimination of ROS Aging (Lv et al., 2021)
Human UCMSCs AMPK/PGC1-signaling-mediated mitochondrial biogenesis Aging sarcopenia (Piao et al., 2022)
Human ADMSCs MiR-19b-3p-mediated regulation of the MST4/ERK/Drp1 signaling pathway Atherosclerosis (Zhang et al., 2023)
Human UCMSCs- EVs Resulted in an enhancement of GPX-1 and extracellular matrix protein Col-1 expression, a reduction in MMP-1 expression Skin photoaging (Deng et al., 2020)
Human UCMSCs In oxidative stress, significant improvements in matrix production and cartilage regeneration. Senile disk degeneration (Khalid et al., 2023)
Human ADMSCs- EVs Anti-inflammatory, antioxidant, gene modifying properties Senile diabetes (Gorgun et al., 2022)
Human PMSCs-Exos miRNA-21 Protects by Targeting the PTEN/PI3K-Nrf2 Axis+ Aging (Xiong et al., 2021)
Human UCMSCs p53/GPX4/SLC7A11 pathway to reduce the level of iron death Ischemic stroke (Zhai et al., 2022)
Human BMSCs-Exos Cellular senescence lncRNA MEG-3 Osteoarthritis in the elderly (Jin et al., 2021)
Rat BMSCs MiR-34a-SIRT1 Cardiomyopathy in aging (Xia and Hou, 2018)
Human UCMSCs-Exos Changes in SASP factors Aging of the kidney (Liao et al., 2021)
Rat BMSCs-Exos Wnt/β-catenin signaling Bone loss (Zuo et al., 2019)
Human ADMSCs- EVs Involvement of miR-146a and Src Senile diabetes (X et al., 2021)
Human UCMSCs Promoting migration, proliferation Senile diabetes wound (Liu et al., 2022a)
Human UCMSCs Altered intercellular communication restored E2 and FSH levels Female reproduction aging (Liu et al., 2022b)
Human ADMSCs-Exos Suppression of PTEN expression by miR-21-5p to modulate follicle number and hormone levels Natural ovarian aging (Grady et al., 2019)
Human BMSCs-Exos Chronic inflammation Brain macrophage infiltration Parkinson’s disease (Dumbrava et al., 2022)
Rat BMSCs-Exos Delivering miR-29c-3p to suppresses BACE1 expression and stimulates the Wnt/−linker pathway Alzheimer’s disease (Sha et al., 2021)
Human HEMSCs-Exos Inhibit IL-1β-induced nitric oxide and MMP13 production Osteoarthritis (Zhang et al., 2019)
Human UCMSCs promoting macrophage polarization toward the M2 phenotype and inhibiting the inflammatory response Osteoarthritis (Jiang et al., 2021)
Human PMSCs Dysbiosis Increase in serum levels of IGFsingle bondI, 3-hydroxybutyrate, glycolic acid, and taurine Ovarian aging (Kim and Lee, 2022)
Human SMSCs Inhibition of the family of MMPs can disrupt the dynamic equilibrium of the ECM Osteoarthritis (Tao et al., 2017)
Human PMSCs MiR-145-5p and BMP-SMAD signaling pathways. Ovarian aging (Kim et al., 2020)
4.1. Improving genomic instability and telomere attrition in aging
The integrity and stability of genomes are frequently compromised by a variety of factors, including errors in DNA replication, chromosome segregation issues, oxidative stress, and spontaneous hydrolysis. These factors can lead to a range of detrimental consequences, such as mutations, deletions, translocations, telomere shortening, chromosomal rearrangements, nuclear structural defects, and gene disruption caused by viral or transposon integration (Vijg and Dong, 2020). Telomere damage is also recognized as a significant contributor to cellular senescence. Over successive cell divisions, telomeres progressively shorten, leading to genomic instability and ultimately triggering apoptosis or senescence (Chakravarti et al., 2021; Blasco, 2005). Conversely, MSCs and their exos have been shown to mitigate genomic instability, thereby slowing down the aging process (Fig. 2).
Fig. 2
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Fig. 2. MSCs can improve aging through genomic instability and telomere attrition. Genomic instability and telomere attrition can lead to aging, and the ability of MSCs to ameliorate these phenomena has been demonstrated in a variety of animal models, including mice and monkeys. In addition to MSCs, exos released from MSCs can also ameliorate genomic instability and thereby ameliorate senescence.

BMSCs and their derived exosomes (Exos) have demonstrated the ability to restore the functionality of senescent stem cells and fibroblasts. Additionally, EVs derived from BMSCs, along with the key DNA repair enzyme Ercc1, have been shown to extend lifespan and alleviate senescence in Ercc1−/− mice (Dorronsoro et al., 2021). In a study by Go et al., EVs obtained from MSCs were found to promote recovery in aged monkeys following cortical injury. This effect was attributed to enhanced myelin sheath formation, reduced DNA damage in oligodendrocytes, and increased density of mature oligodendrocytes post-injury (Go et al., 2021). Another study utilized a doxorubicin (DOXO)-inducible senescence model to explore the impact of stem cell treatment on telomere length and anti-aging effects in Dox-treated H9c2 cells. The findings highlighted the role of the vascular endothelial growth factor (VEGF)/Jagged-1/Notch-1/TGF-β1 signaling pathway in mediating these effects (Chen et al., 2018). Notably, telomere shortening is a significant prognostic marker in elderly patients with Idiopathic Pulmonary Fibrosis (IPF), a severe lung condition. The antifibrotic effects of TGF-β stimulation on bronchoalveolar epithelial cells (A549) and fibroblasts from IPF patients with varying telomere lengths were observed in response to membrane particles (MP) derived from human adipose tissue MSCs. These MPs exhibited senescence-protective properties by upregulating the anti-fibrotic marker TERT in epithelial cells, potentially aiding in the restoration of alveolar structure (Merino et al., 2021).
Inherited defects in DNA repair mechanisms exacerbate DNA damage accumulation, accelerating organ aging in one or multiple systems. While MSCs and their Exos demonstrate notable anti-aging potential, their precise role in the relationship between nuclear DNA damage and aging warrants further investigation and discussion.
4.2. Improving epigenetic alterations and loss in proteostasis
Alterations in DNA methylation patterns (Seale et al., 2022), aberrant post-translational modifications of histones (Lu et al., 2021), abnormal remodeling of chromatin (Swer and Sharma, 2021), and dysfunctional non-coding RNAs (ncRNAs) are among the various epigenetic modifications that contribute to the process of aging (Jusic et al., 2022). Also, the disruption of intracellular protein homeostasis, resulting from an augmented production of inaccurately translated, misfolded, or unfinished proteins, has been implicated in the aging process (Martinez-Miguel et al., 2021; Tsakiri et al., 2013). In contrast, MSCs and Exos have the potential to enhance one or more of these epigenetic alterations, thereby mitigating the effects of aging (Fig. 3).
Fig. 3
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Fig. 3. MSCs can improve aging through epigenetic alterations and loss of proteostasis. Epigenetic alterations and loss of proteostasis can lead to aging, and this role for them has been demonstrated in a variety of aging models including, chronic renal failure in the elderly, aging-associated insulin resistance, and Alzheimer’s disease. MSCs treatment has ameliorated aging conditions to some degree in all cases.

Aging is closely linked to the global depletion of histones and tissue-specific alterations in their post-translational modifications. In a study by Zhang, MSC-Exos were shown to mitigate oxidative damage in H2O2-induced microglia (BV2) in vitro. Additionally, the conditioned medium of UCMSCs was found to counteract high glucose (HG)-induced extracellular matrix degradation in nucleus pulposus mesenchymal stem cells (NPMSCs). Specifically, MSCs-conditioned media (CM) treatment significantly reduced the levels of collagen II and aggrecan in NPMSCs, but these effects were reversed by the activation of phosphorylated p38 MAPK, restoring the extracellular matrix components (Qi et al., 2019). In another report (Cao et al., 2021), Cao et al. reported that miR-133b in MSC-derived extracellular vesicles (MSC-EVs) modulated connective tissue growth factor (CTGF), reducing TGF-2-induced renal cortical proximal tubular epithelial cell (HK1) damage, renal tubular epithelial-mesenchymal transition (EMT), and renal interstitial fibrosis in aged mice. SIRT1 (Sirtuin-1), a gene associated with premature aging, disease, and longevity, encodes a deacetylase enzyme that regulates various epigenetic modifications, influencing gene expression and chromatin structure. MSC-Exos significantly upregulated the expression of the SIRT1 gene in senescent mice (X. Zhang et al., 2023). Yu conducted a study (Yu et al., 2021) which demonstrated that the sustained release of miR-217 inhibitor from MSC-derived EVs played a role in reducing MSC-mediated neointimal hyperplasia following vascular injury. The overexpression of miR-217 resulted in the downregulation of Sirt-1 protein expression, leading to an increase in senescence, ROS expression, and EB malformation in transfected MSCs. Additionally, other studies (Sun et al., 2018) demonstrated that miR-2b targeted Sirtuin-1 in HK133 cells, resulting in increased Sirtuin-1 expression and a reduction in TGF-1-induced EMT and renal fibrosis. The investigation of the intricate relationship between aging-associated insulin resistance remains a prominent area of research. According to a study conducted by Su et al., it was discovered that the release of nanoscale exos miR-29b-3p from BMSCs in aged mice plays a regulatory role in insulin resistance through the activation of SIRT1. This finding suggests that targeting SIRT1 could potentially serve as a therapeutic approach for managing insulin resistance associated with aging (Su et al., 2019). In their study, Jiad et al. found that the activation of the cMet-AKT-GSK3 signaling pathway, along with the downregulation of hyperphosphorylated tau and the promotion of synaptic plasticity in the hippocampus of SAMP8 mice (a mouse model of Alzheimer’s disease with accelerated aging), led to the reversal of spinal loss. Furthermore, the utilization of SAMP8 mice to administer HUCMSCs that secreted hepatocyte growth factor (HGF) was found to modify the improvement of neurofibrillary tangles (NFT) (Jia et al., 2020a).
In vitro studies by Zhang et al. demonstrated that BMSCs could enhance the expression of genes associated with proliferation (PCNA and FGF-2) and anti-apoptosis (survivin and Bcl-2) in chondrocytes. The inhibition of CD73 led to reduced chondrocyte proliferation and increased apoptosis, suggesting that CD73/ecto-5′-nucleotidase plays a critical role in mediating these biological functions (Zhang et al., 2018). Similarly, Exos derived from olfactory mucosal mesenchymal stem cells (OM-MSCs-Exos) were shown to significantly improve cognitive function, reduce neuroinflammatory responses, alleviate endoplasmic reticulum (ER) stress, and decrease neuronal apoptosis in mouse models of Alzheimer’s disease. These effects are thought to be mediated through the involvement of LRP1(Hu et al., 2025).
The strong link between aging and epigenetic alterations, as well as the loss of proteostasis, has garnered considerable attention in the scientific community. Given the reversible nature of epigenetic modifications, these pathways represent promising targets for therapeutic interventions aimed at mitigating age-related decline. In this context, MSCs and Exos have emerged as pivotal tools in the development of anti-aging strategies, offering potential avenues for addressing the multifaceted challenges of aging.
4.3. Improving disabled macroautophagy, mitochondrial dysfunction and chronic inflammation in aging
Loss of macroautophagy, mitochondrial dysfunction, and chronic inflammation are key hallmarks of aging. One of the most significant mechanisms underlying the reduced turnover of organelles is the age-related decline in autophagy (Levine and Kroemer, 2019), Additionally, the deterioration of mitochondrial function with age is driven by a complex interplay of mechanisms, including the accumulation of mitochondrial DNA mutations, dysregulation of protein homeostasis leading to destabilization of the respiratory chain complex, impaired organelle turnover, and alterations in mitochondrial dynamics (Chakravarti et al., 2021; Amorim et al., 2022), These changes can further exacerbate inflammation. Specific alterations in the immune and inflammatory systems have the potential to either accelerate or decelerate aging in certain organ systems (Qian et al., 2021). It has been well-documented that MSCs and Exos play a crucial role in modulating immune function. Through mechanisms such as immunomodulation and the enhancement of mitochondrial function, they hold significant potential to counteract the effects of aging (Fig. 4).
Fig. 4
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Fig. 4. MSCs can improve aging through disabled macroautophagy, mitochondrial dysfunction and chronic inflammation. Macroautophagy, mitochondrial dysfunction and chronic inflammation can lead to aging, among these, inflammation is a key feature that contributes to aging, and inflammation is specifically correlated with almost all aspects of other hallmarks of aging, with numerous age-related diseases associated with this hallmark and some improvement with both MSCs and Exos therapy.

MiR-199a-5p, produced by MSCs, has been shown to inhibit autophagy and enhance the therapeutic efficacy of MSCs-based treatments for idiopathic pulmonary fibrosis in elderly patients by modulating the Sirt1/AMPK signaling pathway (Shi et al., 2021). Cellular senescence is a critical factor influencing liver regeneration, contributing to a higher incidence of severe complications following liver surgery in the elderly. Recent studies have highlighted the potential of MSC-Exos in addressing this issue, primarily through their association with Atg4B-mediated mitophagy, a key protein in autophagy regulation. This mechanism helps restore mitochondrial integrity and function in aging hepatocytes, thereby promoting their proliferation. Additionally, the enrichment of DEAD-Box helicase 5 (DDX5) in UCMSCs-EVs and its interaction with transcription factor E2F1 facilitate the nuclear translocation of DDX5, activating Atg4B expression (J. Zhang et al., 2023). Further research by Zhang demonstrated that MSCs-Exos reduce oxidative stress and exhibit anti-apoptotic effects in the brains of SAMP8 senescent mice (X. Zhang et al., 2023). Similarly, Chen’s study revealed that overexpression of Bmi1 in MSCs confers anti-aging and anti-osteoporosis effects by mitigating oxidative stress and deactivating the p16/p19 signaling pathway (Chen et al., 2019). Beclin-1, a crucial positive regulator of mammalian autophagy, may also be upregulated by MSCs to activate autophagy signaling, thereby ameliorating Parkinson’s disease (Heris et al., 2022). These findings underscore the multifaceted role of MSCs and Exos in modulating autophagy, mitochondrial function, and oxidative stress, offering promising therapeutic strategies for age-related diseases.
Mitochondria have been recognized as key drivers of both chronic inflammation and cell death. The progressive decline in mitochondrial function during senescence significantly contributes to the development of the senescence phenotype, initiating inflammation and cell death through multiple interconnected pathways (J et al., 2019). Adipose-derived MSCs (ADMSCs) have demonstrated the ability to enhance mitochondrial autophagy, leading to the reduction of intracellular reactive oxygen species (ROS) and the improvement of mitochondrial quality. As a result, these MSCs act as regulators of cellular metabolic homeostasis, ultimately delaying the aging process (Lv et al., 2021; Maremanda et al., 2019). The administration of UCMSCs has been shown to counteract age-related muscle loss, likely due to their ability to reduce oxidative stress, apoptosis, and inflammation, while promoting AMPK/PGC1α-signaling-mediated mitochondrial biogenesis (Piao et al., 2022). In Zhang et al.’s study (Y. Zhang et al., 2023), MSC-Exos were found to effectively mitigate vascular smooth muscle cell (VSMC) senescence induced by Ang II. This protective effect was achieved through the downregulation of mitochondrial fission, mediated by miR-19b-3p regulation of the MST4/ERK/Drp1 signaling pathway. Additionally, the study highlighted the detrimental effects of cisplatin on neuronal mitochondria. Counteracting this mitochondrial damage using a small molecule, pifithrin-μ, which inhibits p53 accumulation in mitochondria, may help prevent the formation of tau deposits in the brains of aged mice. These findings underscore the critical role of mitochondrial function in aging and the potential of MSC-based therapies to mitigate age-related cellular damage.
In Deng’s study (Deng et al., 2020), the aging of dermal fibroblasts was primarily induced by ultraviolet B (UVB) radiation. The researchers evaluated the anti-aging effects of MSC-EVs on dermal fibroblasts exposed to UVB-induced photoaging. Treatment with MSC-EVs led to increased expression of glutathione peroxidase 1 (GPX-1) and extracellular matrix protein collagen type 1 (Col-1), reduced expression of matrix metalloproteinase-1 (MMP-1), improved intracellular reactive oxygen species (ROS) levels, and alleviated UVB-induced photoaging. This investigation aligns with the findings of Khalid et al.(Khalid et al., 2023), who noted that aging and degenerative changes in the intervertebral disc (IVD) occur earlier than in other connective tissues. Their study demonstrated a reduction in oxidative stress in intervertebral disc degeneration (IVDD), alongside significant improvements in matrix production and cartilage regeneration. Reactive oxygen species (ROS), such as hydroxyl radicals (OH−), superoxide ions (O₂−), hypochlorite ions (OCl−), and hydrogen peroxide (H₂O₂), are highly reactive and unstable molecules that contribute to cellular damage. Inflammation is a well-established mechanism driving the aging process, and the dysregulation of macrophages, which play a pivotal role in initiating and modulating inflammatory responses, is a key factor in this phenomenon. These studies collectively highlight the potential of MSCs-EVs in mitigating oxidative stress, inflammation, and tissue degeneration associated with aging.
In a study by Gorgun et al., evidence was provided that MSCs-Exos preconditioned with hypoxic inflammatory cytokines effectively mitigated mitochondrial dysfunction in macrophages. This was achieved by reducing lipid peroxidation and inhibiting mitochondrial complex I activity, oxygen consumption, and ATP synthesis associated with age-related injury (Gorgun et al., 2022; Motawea et al., 2020). Given the increased susceptibility of elderly diabetic patients to cardiovascular events, securing a reliable source of MSCs, such as HUCMSCs is critical for addressing the significant health risks they face. In a study conducted by Xiong et al.(Xiong et al., 2021), the administration of miR-21-enriched exosomes derived from human placental MSCs (hPMSC-Exo) demonstrated multiple beneficial effects in elderly diabetic rats. These included alleviating endothelial dysfunction, reducing systolic blood pressure, and exhibiting antioxidant properties. Additionally, miR-21 in hPMSC-Exos was found to mitigate oxidative stress damage, decrease the expression of senescence-associated proteins, and attenuate senescence in Q and CD2 T cells through the PTEN/PI3K-Nrf2 signaling pathway. Furthermore, HUCMSCs were induced into neural stem cells (NSCs) through the addition of growth factors and neuromodulatory protein 1β (NRG1β) during NSC differentiation. This process may regulate the p53/GPX4/SLC7A11 pathway, reducing ferroptosis levels in cells and thereby slowing the progression of ischemic stroke (Zhai et al., 2022).
In elderly rats subjected to permanent distal middle cerebral artery occlusion (MCAO), the administration of small EVs derived from human BMSCs effectively facilitated neuronal recovery and promoted remodeling of the peri-infarct brain region. BMSC-EVs have shown potential in treating Alzheimer’s disease by delivering miR-29c-3p to neurons, which suppresses BACE1 expression and activates the Wnt/β-catenin pathway. This mechanism reduces neuroinflammation and delays disease progression (Sha et al., 2021). Additionally, MSC-derived exosomes (MSC-Exos) have been demonstrated to promote doxorubicin (DO)-mediated bone regeneration in aged rats. This effect is achieved by enhancing the proliferation and osteogenic capacity of BMSCs, with further improvements potentially attributed to immunomodulatory mechanisms (Jia et al., 2020b). In a study conducted by Khalid et al.(Gorgun et al., 2022), the synergistic effect of Sox9 and TGFβ1 was observed to significantly enhance cartilage formation, regeneration, and matrix synthesis in human umbilical cord mesenchymal stem cells (hUCMSCs). This combination also effectively reduced inflammation in intervertebral disc degeneration (IVDD), thereby alleviating degenerative conditions. In the research conducted by Go et al.(Go et al., 2020), the therapeutic potential of MSC-EVs in treating cortical injury was initially explored in aged rhesus monkeys (Macaca mulatta). The findings revealed that neuroinflammation, initially localized to the lesion site, could spread to other brain regions during the chronic phase of inflammation. According to a study conducted by Gorgun et al.(Walberer et al., 2014), MSCs-Exos preconditioned with hypoxic inflammatory cytokines were shown to reduce the expression of TNF-α, iNOS, and NADase CD38, thereby mitigating age-related inflammation. This discovery is particularly relevant given the increasing prevalence of total joint replacement surgeries among elderly individuals, where wear particles from prosthetic implants often trigger chronic inflammation and osteolysis. Kushioka et al. investigated the therapeutic effects of interleukin-4 overproducing mesenchymal stem cells (IL4-MSCs) on chronic inflammation in elderly mice. The results demonstrated that IL4-MSCs significantly reduced osteoclast activity, increased the M2/M1 macrophage ratio, and enhanced alkaline phosphatase (ALP)-positive areas and bone mineral density (BMD) values, highlighting their potential in addressing age-related inflammatory conditions.(Kushioka et al., 2023). In another study by Motawea et al.(Xiong et al., 2021), HUCMSCs were identified as a reliable source of MSCs. When administered to aged diabetic rats, HUCMSCs effectively lowered systolic blood pressure, improved endothelial dysfunction, and exhibited strong anti-inflammatory properties, thereby alleviating symptoms associated with aged diabetes. Exosomes derived from human embryonic mesenchymal stem cells (HEMSCs) have been shown to enhance sulfated glycosaminoglycan (s-GAG) synthesis, which is otherwise inhibited by IL-1β, while also suppressing IL-1β-induced nitric oxide and MMP13 production. These exosomes modulate inflammatory responses and nociceptive behaviors, playing a significant role in the healing of condylar cartilage and subchondral bone in a rat model of temporomandibular joint osteoarthritis (Zhang et al., 2019). Similarly, HUCMSCs have demonstrated the ability to modulate the articular cavity microenvironment in a rat knee osteochondral defect model. This modulation is primarily achieved by promoting macrophage polarization toward the M2 phenotype and inhibiting inflammatory responses, thereby acting as a potential promoter of osteochondral regeneration (Jiang et al., 2021).
The loss of macroautophagy, mitochondrial dysfunction, and chronic inflammation are key drivers of cellular and molecular aging, as well as the onset of age-related diseases. Targeting these mechanisms offers a promising strategy for mitigating the aging process, with MSCs and Exos emerging as highly promising therapeutic tools in the field of anti-aging research.
4.4. Improving cellular senescence in aging
All cell types undergo senescence, a process partially driven by telomere shortening as individuals age. Senescent cells are commonly found in post-mitotic or slowly replicating tissues, such as the heart and brain. Moreover, many age-related disorders are characterized by the localized or tissue-specific accumulation of senescent cells (Gorgoulis et al., 2019). MSC therapy plays a crucial role in addressing cellular senescence, as the introduction of exogenous MSCs has the potential to counteract cellular senescence within the organism (Fig. 5).
Fig. 5
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Fig. 5. MSCs can improve aging through cellular senescence. Cellular senescence is a biological process that manifests itself particularly in certain diseases, especially age-related diseases. Mesenchymal stem cell therapy plays a crucial role in slowing down cellular senescence.

Cellular senescence is a biological process that can lead to detrimental effects, whether in the short-term or long-term. A study (Jin et al., 2021) conducted by researchers revealed that BMSCs-Exos containing lncRNA MEG-3 can alleviate osteoarthritis by promoting the synthesis of type II collagen and inhibiting cellular senescence and apoptosis, thereby preserving the chondrocyte phenotype. Additionally, another investigation (Liao et al., 2021) demonstrated that UCMSC-Exos could prevent senescence in mouse primary tubular epithelial cells (PTEC) by downregulating the expression of senescence markers and senescence-associated secretory phenotype (SASP) factors. Conversely, the expression of miR-199a-5p derived from MSCs has been shown to induce senescence in patients with pulmonary fibrosis through modulation of the Sirt1/AMPK signaling pathway (Lei et al., 2021). Conversely, a reduction in miR-199a-5p levels has been shown to reverse cellular senescence and enhance the therapeutic efficacy of MSCs in treating pulmonary fibrosis (Levine and Kroemer, 2019). Additionally, EVs derived from human placental MSCs can repair capillary dilation, subsequently activating tumor protein P53 and cell cycle-dependent kinase inhibitor 1A (P21) to inhibit cellular senescence (Kou et al., 2022). BMSCs have demonstrated the ability to counteract proliferation inhibition by mitigating DNA damage and oxidative stress, while also reducing cellular senescence and restoring radiation-induced bone loss through activation of the Wnt/β-catenin signaling pathway (Zuo et al., 2019). Furthermore, MSCs-Exos facilitate the downregulation of SIRT1, leading to a gradual increase in acetylated p53 expression over time. This induces the expression of p53 and its downstream molecule p21, ultimately halting the cell cycle and promoting cellular senescence (Matsuoka et al., 2021). These findings underscore the multifaceted role of MSC-derived therapies in modulating cellular senescence and their potential applications in treating age-related conditions (Matsuoka et al., 2021). MSC-EVs effectively enhance the restoration of senescent endothelial cells (ECs) and accelerate wound healing in aged and diabetic animals by promoting angiogenesis. The regulation of functional recovery and wound healing by MSC-EVs is critically dependent on the involvement of miR-146a and Src. The pro-angiogenic and wound-healing effects of miR-146a can be partially enhanced through the dephosphorylation of Src (X et al., 2021). In Kim’s research (Kim et al., 2021), cellular senescence was investigated in mouse and human models of renal stenosis (STK). However, further research is needed to clarify the precise role of cellular senescence in ischemic and renal artery stenosis (RAS)-induced renal injury. Following MSCs treatment, a reduction in renal cell cycle arrest and senescence activity was observed in RAS. In the context of non-healing wounds, human dermal fibroblasts (HDFs) are prone to aging, leading to impaired migration, proliferation, and secretory function.
In Liu’s study (Liu et al., 2022a), MSCs-CM pretreated with interferon (IFN) and tumor necrosis factor (TNF) (referred to as IT MSC-CM) was found to be enriched with growth factors associated with wound healing. In vitro experiments demonstrated that pretreated MSC-CM was more effective than standard MSC-CM in enhancing the migration, proliferation, and activation of HDFs. Chemotherapy drugs, such as doxorubicin (DOXO), are widely used in cancer treatment but can induce cellular senescence in heart cells, leading to significant cardiotoxicity as a side effect.
In a study conducted by Xia et al., stem cell treatment in rat embryonic myoblasts (H9c2) reduced the expression of senescence-related genes, p53 and p16, and identified the miR-34a-SIRT1 protein axis as a potential mediator of the anti-aging effects of MSCs (Xia and Hou, 2018).
4.5. Altered intercellular communication and dysbiosis
The decline in intercellular communication during aging can significantly disrupt hormone regulation and homeostasis. While the senescence-associated secretory phenotype (SASP) extensively addresses this phenomenon, it is primarily driven by cell-intrinsic factors (Deng et al., 2021; Miller et al., 2020). This review compares MSCs and exosomes (exos), which exhibit either pro-senescence or life-extending properties, with systemic factors transported through the bloodstream. Furthermore, it explores the functioning of various intercellular communication networks and assesses the role of extracellular matrix degradation in the aging process.
In Liu’s study (Liu et al., 2022b), the transplantation of HUCMSCs effectively restored estradiol (E2) and follicle-stimulating hormone (FSH) levels in both aging mice and chemotherapy-induced mice. Additionally, hUCMSC treatment increased the number of primordial follicles, developing follicles, and preovulatory follicles in the ovaries of mice. It also promoted the repair of oviducts and uterine tissues by regenerating oviductal cilia and reconstructing uterine glands and endometrial structures. In the study conducted by Li et al. (Li et al., 2023; Grady et al., 2019), the effects of hUCMSC-derived exosomes (hUCMSC-Exos) on a natural ovarian aging (NOA) mouse model were investigated. The results demonstrated that hUCMSC-Exos could regulate follicle number and hormone levels by inhibiting apoptosis, achieved through the suppression of PTEN expression by miR-21-5p. In Kim’s study (Kim and Lee, 2022), treatment with human placental-derived mesenchymal stem cells (hPD-MSCs) significantly increased serum levels of insulin-like growth factor-I (IGFsingle bondI), a known promoter of healthy lifespan. Additionally, hPD-MSC stimulation elevated levels of 3-hydroxybutyrate, glycolic acid, and taurine, which are associated with improved health and longevity. In the study conducted by Kim (Kim et al., 2020), intravenous administration of human placenta-derived mesenchymal stem cells (hPDMSCs) was shown to enhance ovarian function in older women. This improvement was mediated by miR-145-5p and the BMP-SMAD signaling pathways, highlighting the therapeutic potential of hPDMSCs in addressing age-related ovarian dysfunction. MiR-140-5p in synovial mesenchymal stem cell (SMSCs)-Exos plays a crucial role in inhibiting the matrix metalloproteinase (MMP) family, thereby disrupting the dynamic equilibrium of the extracellular matrix and slowing the progression of osteoarthritis (OA). Conversely, exosomes isolated from synovial fluid have been shown to stimulate the release of inflammatory cytokines and MMPs, highlighting the dual role of exosomes in modulating ECM homeostasis and inflammation in OA (Tao et al., 2017).
5. Clinical trials of mesenchymal stem cells and exosomes for aging
Research on the therapeutic effects of MSCs has progressed from preclinical studies to clinical trials, with ongoing investigations into their potential for treating aging and age-related diseases such as osteoarthritis and Alzheimer’s disease (Table 2).
Table 2. Clinical trials of mesenchymal stem cells and exosomes for aging.

Trial registration Source of MSC Disease Injection method Number of patients Follow-up (years) Results Reference
NCT04240873 BMSCs Osteoarthritis Intra-articular injections 23 1 Significant reductions in WOMAC and KOOS pain scores and prevented radiographic progression of degenerative knee cartilag. (Lee et al., 2025)
NCT05827757 ADMSCs Inflammatory Aging Related Diseases Intravenous injection 12 0.5 Inflammatory cytokines IL-1α, IL-1β, IL-8, IL-6 and TNF-α were significantly decreased and IL-4/IL-10 was increased after MSC injection. (Nguyen et al., 2024)
NCT04314011 HUCMSCs Aging frailty Related Diseases Intravenous injection 30 2 The significant decrease in TNF-α and IL-17, along with the observed improvements in quality of life and physical performance after MSC injection. (Zhu et al., 2024)
NCT05233774 BMSCs Alzheimer’s disease Intravenous injection 120 1.5 The decline in whole-brain volume by 48.4 % for all treatment groups combined, left hippocampal volume by 61.9 %, and reduced neuroinflammation as measured by diffusion tensor imaging. (Rash et al., 2025)
NCT01678534 ADMSCs Stroke Intravenous injection 13 2 Trend toward lower NIHSS scores in the ADMSC-treated group of patients occurring in patients. (de Celis-Ruiz et al., 2022)
Inflammatory aging is strongly linked to age-related diseases such as Alzheimer’s disease, Parkinson’s disease, and atherosclerosis. A clinical study involving 12 patients with aging-related inflammation demonstrated significant reductions in pro-inflammatory cytokine levels (e.g., IL-1α, IL-1β, IL-6, IL-8, and TNF-α) after 180 days of intravenous administration of ADMSCs. The study also confirmed the safety of stem cell therapy for patients with aging-related inflammation, underscoring its potential as a treatment for inflammatory age-related diseases (Nguyen et al., 2024). Frailty, a common geriatric syndrome, is characterized by increased vulnerability to stressors due to diminished physiological reserves across multiple systems (Clegg et al., 2013). In a clinical trial focused on frailty in aging, 30 patients exhibited significant improvements in quality of life and physical function six months after intravenous administration of HUCMSCs. Key indicators such as timed up-and-go, 4-m walking test, and grip strength showed notable enhancements (Zhu et al., 2024). These findings suggest that HUCMSC therapy holds promise as a potential treatment for age-related frailty, offering a novel approach to improving the health and well-being of elderly patients.
In clinical trials targeting Alzheimer’s disease, a neurologically related condition, the transplantation of BMSCs in 120 patients led to significant improvements in brain volume and cognitive deficits. The treatment demonstrated a favorable safety profile, with no serious adverse effects reported (Rash et al., 2025). Similarly, intravenous infusion of AD-MSCs in a rat model of stroke yielded promising results, including functional recovery, reduced cell death in brain tissue, and increased cell proliferation in the peri-infarct region, all without safety concerns (Gutiérrez-Fernández et al., 2015). In a clinical study involving 13 patients, the ADMSC treatment group showed a trend toward lower National Institutes of Health Stroke Scale (NIHSS) scores. However, no significant difference in functional outcomes was observed based on the modified Rankin Scale (mRS). This outcome was likely influenced by the small sample size, a limitation inherent to the pilot nature of the trial. Nonetheless, the treatment was found to be safe for all participants (de Celis-Ruiz et al., 2022).
OA of the knee is a complex degenerative joint disease characterized by the deterioration of articular cartilage, leading to damage of joint tissues and subsequent impairment of joint function (Cross et al., 2014). In a clinical trial targeting this condition, a single intra-articular injection of allogeneic BMSCs in 23 patients safely alleviated pain and significantly reduced pain scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Additionally, the treatment demonstrated the potential to prevent the progression of degenerative knee cartilage damage, as evidenced by imaging studies (Lee et al., 2025).
Clinical trials of MSCs-based therapies have expanded the search for innovative treatments for various diseases. However, several challenges remain unresolved, including ethical considerations, the translation of basic research findings into clinical applications, and potential adverse effects of treatments. Significant technological and methodological barriers must be addressed to transform fundamental discoveries in stem cell biology into safe and effective clinical therapies. As a type of pluripotent stem cell, MSCs hold immense promise in regenerative medicine and cell therapy. Despite existing challenges in clinical applications, ongoing research and technological advancements are expected to position MSCs as a pivotal tool for treating a wide range of diseases in the future. By optimizing MSCs production and application techniques, and integrating them with personalized medicine approaches, MSCs are poised to offer new therapeutic hope for patients worldwide.
6. Future prospect
Aging has emerged as a critical global public health issue, with recent animal studies highlighting the anti-aging potential of MSCs. Compared to conventional drug therapies, MSCs offer distinct advantages, including easy accessibility, low immunogenicity, and exceptional potential for multilineage differentiation. While MSCs exert diverse biological effects, the paracrine mechanism is considered one of the most important drivers of their therapeutic impact. The influence of MSCs and their Exos on aging is multifaceted, with growing evidence supporting their potential in treating various age-related diseases. However, it is important to note that MSCs may also play a role in promoting aging under certain conditions. Currently, several aging markers have been identified, and MSCs and their exos have shown the ability to modulate these markers, potentially slowing the aging process. These findings underscore the dual role of MSCs in aging and their promise as a therapeutic tool for age-related conditions.
Despite the significant potential of pluripotent stem cells in mitigating and reversing the aging process, stem cell therapy faces several limitations. These include the tumorigenic potential (Bozorgmehr et al., 2020) and genetic instability (Zhou et al., 2021) of MSCs, alongside the diminished therapeutic efficacy arising from MSC impairment (Mai et al., 2021). Exos, as paracrine factors secreted by MSCs, not only mediate the therapeutic effects of MSCs but also exhibit stem cell-like properties while overcoming some of these limitations. Consequently, exos hold promise as a potential alternative to MSCs for treating specific diseases in the future. A major challenge in MSCs therapy is the heterogeneity of adult tissue-derived MSCs, which complicates quality control. Ensuring consistent quality across MSCs from different donors, including their exos, remains difficult. Therefore, stringent quality control measures are essential to minimize batch-to-batch variability (Lian et al., 2010). To address these challenges, pluripotent stem cell-derived MSCs have been proposed as a more standardized alternative. Notably, GMP-grade MSCs derived from pluripotent stem cells have already been utilized in clinical trials for refractory graft-versus-host disease (GVHD) (Bloor et al., 2020). However, their potential role in slowing down aging remains an area for further exploration. These advancements highlight the need for continued research to optimize MSCs and Exos based therapies for aging and age-related diseases.
Current research is centered on understanding the role of MSCs and their Exos in slowing down the aging process. This research not only explores well-established hallmarks of aging but also highlights the need to investigate additional, less-understood aspects of aging. It is important to recognize that the hallmarks of aging are interconnected rather than isolated, with each characteristic closely influencing and interacting with others. By elucidating the direct relationships between these hallmarks, MSCs and their exos offer valuable insights and potential strategies for delaying aging. These findings underscore the complexity of aging and the multifaceted therapeutic potential of MSC-based interventions.
7. Conclusion
The therapeutic potential of MSCs in ameliorating aging is highly promising, but further exploration of their mechanisms of action and broader applications is essential. MSC-exos are a key factor contributing to the positive effects of MSCs, and it remains to be determined whether cell-free therapies can serve as a viable alternative to MSCs treatments. While MSC therapy has shown efficacy in addressing inflammation in certain clinical diseases, its role in the field of aging remains to be fully examined. This review comprehensively outlines the mechanisms and limitations of MSCs and their exosomes in delaying aging and mitigating age-related diseases, providing valuable insights and references for future MSCs therapies in the context of aging.
Abbreviations
BMSCs
Bone marrow mesenchymal stem cells
Exos
Exosomes
TFAM
Mitochondrial transcription factor A
mtDNA
Mitochondrial DNA
iPSCs
Induced pluripotent stem cells
NPCs
Nucleus pulposus cells
DMSCs
Adipose mesenchymal stem cells
MP
Membrane particles
UCMSCs
Umbilical cord mesenchymal stem cells
CTGF
Tissue growth factor
EMT
Epithelial-mesenchymal transition
OM-MSCs
Olfactory mucosa mesenchymal stem cells
DDX5
DEAD-Box helicase 5
E2F1
E2F transcription factor 1
ROS
Reactive oxygen species
GPX-1
Glutathione peroxidase 1
MMP-1
Matrix metalloproteinase-1
Col-1
Collagen type 1
SASP
Senescence-associated secretory phenotype
PMSCs
Placenta mesenchymal stem cells
FSH
Follicle-stimulating hormone
IL-1α
Interleukin 1α
CRediT authorship contribution statement
Dongfeng Lan: Writing – original draft. Dan Zhang: Conceptualization. Xiaofang Dai: Formal analysis. Ji Cai: Funding acquisition. He Zhou: Formal analysis. Tao Song: Methodology. Xianyao Wang: Resources. Qinghong Kong: Validation. Zhengzhen Tang: Formal analysis. Jun Tan: Writing – review & editing. Jidong Zhang: Writing – review & editing.
Consent for publication
All figures and tables in this manuscript are original and all authors approved the submission.
Ethical approval and consent to participate
Not applicable.
Funding
This work was supported by the National Nature Science Foundation of China (NSFC. 31960156, 31660338, 32270848); the Collaborative Innovation Center of Chinese Ministry of Education (2020-39); the Science and Technology Support Program of Guizhou Province (QKH[2020]4Y192, QKH[2019]5406, QKH-ZK[2021]111); and the Science and Technology Fund of Guizhou Provincial Health Commission (gzwkj2022-019).
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this review.
Acknowledgments
Not applicable.
Data availability
Not applicable.
References
Ahmadi and Rezaie, 2021
M. Ahmadi, J. Rezaie
Ageing and mesenchymal stem cells derived exosomes: molecular insight and challenges
Cell Biochem. Funct., 39 (2021), pp. 60-66, 10.1002/cbf.3602
View in ScopusGoogle Scholar
Amorim et al., 2022
J.A. Amorim, G. Coppotelli, A.P. Rolo, C.M. Palmeira, J.M. Ross, D.A. Sinclair
Mitochondrial and metabolic dysfunction in ageing and age-related diseases
Nat. Rev. Endocrinol., 18 (2022), pp. 243-258, 10.1038/s41574-021-00626-7
View in ScopusGoogle Scholar
Anel et al., 2019
A. Anel, A. Gallego-Lleyda, D. de Miguel, J. Naval, L. Martínez-Lostao
Role of exosomes in the regulation of T-cell mediated immune responses and in autoimmune disease
Cells, 8 (2019), p. 154, 10.3390/cells8020154
View in ScopusGoogle Scholar
Asmussen et al., 2019
N. Asmussen, Z. Lin, M.J. McClure, Z. Schwartz, B.D. Boyan
Regulation of extracellular matrix vesicles via rapid responses to steroid hormones during endochondral bone formation
Steroids, 142 (2019), pp. 43-47, 10.1016/j.steroids.2017.12.003
View PDF
View articleView in ScopusGoogle Scholar
Blasco, 2005
M.A. Blasco
Telomeres and human disease: ageing, cancer and beyond
Nat. Rev. Genet., 6 (2005), pp. 611-622, 10.1038/nrg1656
View in ScopusGoogle Scholar
Bloor et al., 2020
A.J.C. Bloor, A. Patel, J.E. Griffin, M.H. Gilleece, R. Radia, D.T. Yeung, D. Drier, L.S. Larson, G.I. Uenishi, D. Hei, K. Kelly, I. Slukvin, J.E.J. Rasko
Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study
Nat. Med., 26 (2020), pp. 1720-1725, 10.1038/s41591-020-1050-x
View in ScopusGoogle Scholar
Bozorgmehr et al., 2020
M. Bozorgmehr, S. Gurung, S. Darzi, S. Nikoo, S. Kazemnejad, A.-H. Zarnani, C.E. Gargett
Endometrial and menstrual blood mesenchymal stem/stromal cells: biological properties and clinical application
Front Cell Dev Biol, 8 (2020), p. 497, 10.3389/fcell.2020.00497
View in ScopusGoogle Scholar
Brosh, 2013
R.M. Brosh
DNA helicases involved in DNA repair and their roles in cancer
Nat. Rev. Cancer, 13 (2013), pp. 542-558, 10.1038/nrc3560
View in ScopusGoogle Scholar
Campisi et al., 2019
J. Campisi, P. Kapahi, G.J. Lithgow, S. Melov, J.C. Newman, E. Verdin
From discoveries in ageing research to therapeutics for healthy ageing
Nature, 571 (2019), pp. 183-192, 10.1038/s41586-019-1365-2
View in ScopusGoogle Scholar
Cao et al., 2021
D. Cao, Y. Wang, Yingjie Zhang, Yinping Zhang, Q. Huang, Z. Yin, G. Cai, X. Chen, X. Sun
Regulation of connective tissue growth factor expression by miR-133b for the treatment of renal interstitial fibrosis in aged mice with unilateral ureteral obstruction
Stem Cell Res Ther, 12 (2021), p. 171, 10.1186/s13287-021-02210-2
Google Scholar
de Celis-Ruiz et al., 2022
E. de Celis-Ruiz, B. Fuentes, M. Alonso de Leciñana, M. Gutiérrez-Fernández, A.M. Borobia, R. Gutiérrez-Zúñiga, G. Ruiz-Ares, L. Otero-Ortega, F. Laso-García, M.C. Gómez-de Frutos, E. Díez-Tejedor
Final results of allogeneic adipose tissue–derived mesenchymal stem cells in acute ischemic stroke (AMASCIS): a phase II, randomized, double-blind, placebo-controlled, single-center
Pilot Clinical Trial. Cell Transplant, 31 (2022), Article 09636897221083863, 10.1177/09636897221083863
Google Scholar
Chakravarti et al., 2021
D. Chakravarti, K.A. LaBella, R.A. DePinho
Telomeres: history, health, and hallmarks of aging
Cell, 184 (2021), pp. 306-322, 10.1016/j.cell.2020.12.028
View PDF
View articleView in ScopusGoogle Scholar
Chen et al., 2016
W. Chen, Y. Huang, J. Han, L. Yu, Y. Li, Z. Lu, H. Li, Z. Liu, C. Shi, F. Duan, Y. Xiao
Immunomodulatory effects of mesenchymal stromal cells-derived exosomes
Immunol. Res., 64 (2016), pp. 831-840, 10.1007/s12026-016-8798-6
Google Scholar
Chen et al., 2018
L. Chen, W. Xia, M. Hou
Mesenchymal stem cells attenuate doxorubicin-induced cellular senescence through the VEGF/Notch/TGF-β signaling pathway in H9c2 cardiomyocytes
Int. J. Mol. Med., 42 (2018), pp. 674-684, 10.3892/ijmm.2018.3635
View in ScopusGoogle Scholar
Chen et al., 2019
G. Chen, Y. Zhang, S. Yu, W. Sun, D. Miao
Bmi1 overexpression in mesenchymal stem cells exerts antiaging and antiosteoporosis effects by inactivating p16/p19 signaling and inhibiting oxidative stress
Stem Cells, 37 (2019), pp. 1200-1211, 10.1002/stem.3007
Google Scholar
Clegg et al., 2013
A. Clegg, J. Young, S. Iliffe, M.O. Rikkert, K. Rockwood
Frailty in elderly people
Lancet, 381 (2013), pp. 752-762, 10.1016/S0140-6736(12)62167-9
View PDF
View articleView in ScopusGoogle Scholar
Cross et al., 2014
M. Cross, E. Smith, D. Hoy, S. Nolte, I. Ackerman, M. Fransen, L. Bridgett, S. Williams, F. Guillemin, C.L. Hill, L.L. Laslett, G. Jones, F. Cicuttini, R. Osborne, T. Vos, R. Buchbinder, A. Woolf, L. March
The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study
Ann. Rheum. Dis., 73 (2014), pp. 1323-1330, 10.1136/annrheumdis-2013-204763
View PDF
View articleView in ScopusGoogle Scholar
Demonbreun and McNally, 2017
A.R. Demonbreun, E.M. McNally
Muscle cell communication in development and repair
Curr. Opin. Pharmacol., 34 (2017), pp. 7-14, 10.1016/j.coph.2017.03.008
View PDF
View articleView in ScopusGoogle Scholar
Deng et al., 2020
M. Deng, T.Z. Yu, D. Li, X. Wang, G. Zhou, W. Liu, Y. Cao, W. Xia, W. Li, W.J. Zhang
Human umbilical cord mesenchymal stem cell-derived and dermal fibroblast-derived extracellular vesicles protect dermal fibroblasts from ultraviolet radiation-induced photoaging in vitro
Photochem. Photobiol. Sci., 19 (2020), pp. 406-414, 10.1039/c9pp00421a
View in ScopusGoogle Scholar
Deng et al., 2021
P. Deng, Q. Yuan, Y. Cheng, J. Li, Z. Liu, Y. Liu, Y. Li, T. Su, J. Wang, M.E. Salvo, W. Wang, G. Fan, K. Lyons, B. Yu, C.-Y. Wang
Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging
Cell Stem Cell, 28 (2021), pp. 1057-1073, 10.1016/j.stem.2021.01.010
View in ScopusGoogle Scholar
Dorronsoro et al., 2021
A. Dorronsoro, F.E. Santiago, D. Grassi, T. Zhang, R.C. Lai, S.J. McGowan, L. Angelini, M. Lavasani, L. Corbo, A. Lu, R.W. Brooks, M. Garcia-Contreras, D.B. Stolz, A. Amelio, S.V. Boregowda, M. Fallahi, A. Reich, C. Ricordi, D.G. Phinney, J. Huard, S.K. Lim, L.J. Niedernhofer, P.D. Robbins
Mesenchymal stem cell-derived extracellular vesicles reduce senescence and extend health span in mouse models of aging
Aging Cell, 20 (2021), Article e13337, 10.1111/acel.13337
View in ScopusGoogle Scholar
Du et al., 2014
W.W. Du, W. Yang, L. Fang, J. Xuan, H. Li, A. Khorshidi, S. Gupta, X. Li, B.B. Yang
miR-17 extends mouse lifespan by inhibiting senescence signaling mediated by MKP7
Cell Death Dis., 5 (2014), Article e1355, 10.1038/cddis.2014.305
View in ScopusGoogle Scholar
Dumbrava et al., 2022
D.-A. Dumbrava, R. Surugiu, V. Börger, M. Ruscu, T. Tertel, B. Giebel, D.M. Hermann, A. Popa-Wagner
Mesenchymal stromal cell-derived small extracellular vesicles promote neurological recovery and brain remodeling after distal middle cerebral artery occlusion in aged rats
Geroscience, 44 (2022), pp. 293-310, 10.1007/s11357-021-00483-2
View in ScopusGoogle Scholar
Fraile et al., 2022
M. Fraile, N. Eiro, L.A. Costa, A. Martín, F.J. Vizoso
Aging and mesenchymal stem cells: basic concepts
Challenges and Strategies. Biology (Basel), 11 (2022), p. 1678, 10.3390/biology11111678
View in ScopusGoogle Scholar
Go et al., 2020
V. Go, B.G.E. Bowley, M.A. Pessina, Z.G. Zhang, M. Chopp, S.P. Finklestein, D.L. Rosene, M. Medalla, B. Buller, T.L. Moore
Extracellular vesicles from mesenchymal stem cells reduce microglial-mediated neuroinflammation after cortical injury in aged Rhesus monkeys
Geroscience, 42 (2020), pp. 1-17, 10.1007/s11357-019-00115-w
View in ScopusGoogle Scholar
Go et al., 2021
V. Go, D. Sarikaya, Y. Zhou, B.G.E. Bowley, M.A. Pessina, D.L. Rosene, Z.G. Zhang, M. Chopp, S.P. Finklestein, M. Medalla, B. Buller, T.L. Moore
Extracellular vesicles derived from bone marrow mesenchymal stem cells enhance myelin maintenance after cortical injury in aged rhesus monkeys
Exp. Neurol., 337 (2021), Article 113540, 10.1016/j.expneurol.2020.113540
View PDF
View articleView in ScopusGoogle Scholar
Gorgoulis et al., 2019
V. Gorgoulis, P.D. Adams, A. Alimonti, D.C. Bennett, O. Bischof, C. Bishop, J. Campisi, M. Collado, K. Evangelou, G. Ferbeyre, J. Gil, E. Hara, V. Krizhanovsky, D. Jurk, A.B. Maier, M. Narita, L. Niedernhofer, J.F. Passos, P.D. Robbins, C.A. Schmitt, J. Sedivy, K. Vougas, T. von Zglinicki, D. Zhou, M. Serrano, M. Demaria
Cellular senescence: defining a path forward
Cell, 179 (2019), pp. 813-827, 10.1016/j.cell.2019.10.005
View PDF
View articleView in ScopusGoogle Scholar
Gorgun et al., 2022
C. Gorgun, C. Africano, M.C. Ciferri, N. Bertola, D. Reverberi, R. Quarto, S. Ravera, R. Tasso
Preconditioned mesenchymal stromal cell-derived extracellular vesicles (EVs) counteract inflammaging
Cells, 11 (2022), p. 3695, 10.3390/cells11223695
View in ScopusGoogle Scholar
Grady et al., 2019
S.T. Grady, A.E. Watts, J.A. Thompson, M.C.T. Penedo, K. Konganti, K. Hinrichs
Effect of intra-ovarian injection of mesenchymal stem cells in aged mares
J. Assist. Reprod. Genet., 36 (2019), pp. 543-556, 10.1007/s10815-018-1371-6
View in ScopusGoogle Scholar
Gutiérrez-Fernández et al., 2015
M. Gutiérrez-Fernández, L. Otero-Ortega, J. Ramos-Cejudo, B. Rodríguez-Frutos, B. Fuentes, E. Díez-Tejedor
Adipose tissue-derived mesenchymal stem cells as a strategy to improve recovery after stroke
Expert. Opin. Biol. Ther., 15 (2015), pp. 873-881, 10.1517/14712598.2015.1040386
View in ScopusGoogle Scholar
H Rashed et al., 2017
M. H Rashed, E. Bayraktar, G. K Helal, M.F. Abd-Ellah, P. Amero, A. Chavez-Reyes, C. Rodriguez-Aguayo
Exosomes: from garbage bins to promising therapeutic targets
Int. J. Mol. Sci., 18 (2017), p. 538, 10.3390/ijms18030538
Google Scholar
Hade et al., 2021
M.D. Hade, C.N. Suire, Z. Suo
Mesenchymal stem cell-derived exosomes: applications in regenerative medicine
Cells, 10 (2021), p. 1959, 10.3390/cells10081959
View in ScopusGoogle Scholar
He et al., 2018
C. He, S. Zheng, Y. Luo, B. Wang
Exosome theranostics: biology and translational medicine
Theranostics, 8 (2018), pp. 237-255, 10.7150/thno.21945
View in ScopusGoogle Scholar
Heris et al., 2022
R.M. Heris, M. Shirvaliloo, S. Abbaspour-Aghdam, A. Hazrati, A. Shariati, H.R. Youshanlouei, F.J. Niaragh, H. Valizadeh, M. Ahmadi
The potential use of mesenchymal stem cells and their exosomes in Parkinson’s disease treatment
Stem Cell Res Ther, 13 (2022), p. 371, 10.1186/s13287-022-03050-4
View in ScopusGoogle Scholar
Hisamatsu et al., 2016
D. Hisamatsu, M. Ohno-Oishi, S. Nakamura, Y. Mabuchi, H. Naka-Kaneda
Growth differentiation factor 6 derived from mesenchymal stem/stromal cells reduces age-related functional deterioration in multiple tissues
Aging (Albany NY), 8 (2016), pp. 1259-1275, 10.18632/aging.100982
View in ScopusGoogle Scholar
Hou et al., 2019
Y. Hou, X. Dan, M. Babbar, Y. Wei, S.G. Hasselbalch, D.L. Croteau, V.A. Bohr
Ageing as a risk factor for neurodegenerative disease
Nat. Rev. Neurol., 15 (2019), pp. 565-581, 10.1038/s41582-019-0244-7
View in ScopusGoogle Scholar
Hu et al., 2022
H. Hu, H. Zhang, Z. Bu, Z. Liu, F. Lv, M. Pan, X. Huang, L. Cheng
Small extracellular vesicles released from bioglass/hydrogel scaffold promote vascularized bone regeneration by transferring miR-23a-3p
Int. J. Nanomedicine, 17 (2022), pp. 6201-6220, 10.2147/IJN.S389471
View in ScopusGoogle Scholar
Hu et al., 2025
X. Hu, Y.-N. Ma, J. Peng, Z. Wang, Y. Liang, Y. Xia
Exosomes derived from olfactory mucosa mesenchymal stem cells attenuate cognitive impairment in a mouse model of Alzheimer’s disease
Biosci. Trends. (2025), 10.5582/bst.2025.01065
Google Scholar
Huang et al., 2023
H. Huang, X. Liu, J. Wang, M. Suo, J. Zhang, T. Sun, W. Zhang, Z. Li
Umbilical cord mesenchymal stem cells for regenerative treatment of intervertebral disc degeneration
Front Cell Dev Biol, 11 (2023), Article 1215698, 10.3389/fcell.2023.1215698
View in ScopusGoogle Scholar
Isaac et al., 2021
R. Isaac, F.C.G. Reis, W. Ying, J.M. Olefsky
Exosomes as mediators of intercellular crosstalk in metabolism
Cell Metab., 33 (2021), pp. 1744-1762, 10.1016/j.cmet.2021.08.006
View PDF
View articleView in ScopusGoogle Scholar
J et al., 2019
M. J, L. J, N. J, Z. Y, S. W, C. Luo, L. Y, C. Li, L. H, Y. P, L. Y, H. Ff, Z. L
Wnt/β-catenin/RAS signaling mediates age-related renal fibrosis and is associated with mitochondrial dysfunction
Aging Cell, 18 (2019), 10.1111/acel.13004
Google Scholar
Jia et al., 2020a
Yali Jia, N. Cao, J. Zhai, Q. Zeng, P. Zheng, R. Su, T. Liao, J. Liu, H. Pei, Z. Fan, J. Zhou, J. Xi, L. He, L. Chen, X. Nan, W. Yue, X. Pei
HGF mediates clinical-grade human umbilical cord-derived mesenchymal stem cells improved functional recovery in a senescence-accelerated mouse model of Alzheimer’s disease
Adv Sci (Weinh), 7 (2020), Article 1903809, 10.1002/advs.201903809
View in ScopusGoogle Scholar
Jia et al., 2020b
Yachao Jia, S. Qiu, J. Xu, Q. Kang, Y. Chai
Exosomes secreted by young mesenchymal stem cells promote new bone formation during distraction osteogenesis in older rats
Calcif. Tissue Int., 106 (2020), pp. 509-517, 10.1007/s00223-019-00656-4
Google Scholar
Jiang et al., 2021
S. Jiang, G. Tian, Z. Yang, X. Gao, F. Wang, J. Li, Z. Tian, B. Huang, F. Wei, X. Sang, L. Shao, J. Zhou, Z. Wang, S. Liu, X. Sui, Q. Guo, W. Guo, X. Li
Enhancement of acellular cartilage matrix scaffold by Wharton’s jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration
Bioact Mater, 6 (2021), pp. 2711-2728, 10.1016/j.bioactmat.2021.01.031
View PDF
View articleView in ScopusGoogle Scholar
Jin et al., 2021
Y. Jin, M. Xu, H. Zhu, C. Dong, J. Ji, Y. Liu, A. Deng, Z. Gu
Therapeutic effects of bone marrow mesenchymal stem cells-derived exosomes on osteoarthritis
J. Cell. Mol. Med., 25 (2021), pp. 9281-9294, 10.1111/jcmm.16860
View in ScopusGoogle Scholar
Jusic et al., 2022
A. Jusic, P.B. Thomas, S.B. Wettinger, S. Dogan, R. Farrugia, C. Gaetano, B.G. Tuna, F. Pinet, E.L. Robinson, S. Tual-Chalot, K. Stellos, Y. Devaux, EU-CardioRNA COST Action CA17129
Noncoding RNAs in age-related cardiovascular diseases
Ageing Res. Rev., 77 (2022), Article 101610, 10.1016/j.arr.2022.101610
View PDF
View articleView in ScopusGoogle Scholar
Khalid et al., 2023
S. Khalid, S. Ekram, F. Ramzan, A. Salim, I. Khan
Co-regulation of Sox9 and TGFβ1 transcription factors in mesenchymal stem cells regenerated the intervertebral disc degeneration
Front. Med. (Lausanne), 10 (2023), Article 1127303, 10.3389/fmed.2023.1127303
View in ScopusGoogle Scholar
Khaltourina et al., 2020
D. Khaltourina, Y. Matveyev, A. Alekseev, F. Cortese, A. Ioviţă
Aging fits the disease criteria of the International Classification of Diseases
Mech. Ageing Dev., 189 (2020), Article 111230, 10.1016/j.mad.2020.111230
View PDF
View articleView in ScopusGoogle Scholar
Kim and Lee, 2022
K.-H. Kim, K.-A. Lee
Metabolic rewiring by human placenta-derived mesenchymal stem cell therapy promotes rejuvenation in aged female rats
Int. J. Mol. Sci., 23 (2022), p. 566, 10.3390/ijms23010566
View in ScopusGoogle Scholar
Kim et al., 2020
K.-H. Kim, E.-Y. Kim, G.J. Kim, J.-J. Ko, K.Y. Cha, M.K. Koong, K.-A. Lee
Human placenta-derived mesenchymal stem cells stimulate ovarian function via miR-145 and bone morphogenetic protein signaling in aged rats
Stem Cell Res Ther, 11 (2020), p. 472, 10.1186/s13287-020-01988-x
Google Scholar
Kim et al., 2021
S.R. Kim, X. Zou, H. Tang, A.S. Puranik, A.M. Abumoawad, X.-Y. Zhu, L.J. Hickson, T. Tchkonia, S.C. Textor, J.L. Kirkland, L.O. Lerman
Increased cellular senescence in the murine and human stenotic kidney: Effect of mesenchymal stem cells
J. Cell. Physiol., 236 (2021), pp. 1332-1344, 10.1002/jcp.29940
View in ScopusGoogle Scholar
Kou et al., 2022
M. Kou, L. Huang, J. Yang, Z. Chiang, S. Chen, J. Liu, L. Guo, X. Zhang, X. Zhou, X. Xu, X. Yan, Y. Wang, J. Zhang, A. Xu, H.-F. Tse, Q. Lian
Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?
Cell Death Dis., 13 (2022), p. 580, 10.1038/s41419-022-05034-x
View in ScopusGoogle Scholar
Kushioka et al., 2023
J. Kushioka, M. Toya, H. Shen, H. Hirata, N. Zhang, E. Huang, M. Tsubosaka, Q. Gao, V. Teissier, X. Li, T. Utsunomiya, S.B. Goodman
Therapeutic effects of MSCs, genetically modified MSCs, and NFĸB-inhibitor on chronic inflammatory osteolysis in aged mice
J. Orthop. Res., 41 (2023), pp. 1004-1013, 10.1002/jor.25434
View in ScopusGoogle Scholar
Lavretsky, 2023
H. Lavretsky
Presidential address: Reimagining the field of geriatric psychiatry in the 2020–2030 decade of healthy aging: focus on innovation to promote brain health and well-being in aging adults and caregivers
Am. J. Geriatr. Psychiatry, 31 (2023), pp. 1011-1016, 10.1016/j.jagp.2023.08.008
View PDF
View articleView in ScopusGoogle Scholar
Lee et al., 2025
B.-W. Lee, J.J. Lee, J.-Y. Jung, J.H. Ju
Intra-articular injection of human bone marrow–derived mesenchymal stem cells in knee osteoarthritis: a randomized, double-blind, controlled trial
Cell Transplant., 34 (2025), Article 09636897241303275, 10.1177/09636897241303275
Google Scholar
Lei et al., 2021
X. Lei, N. He, L. Zhu, M. Zhou, K. Zhang, C. Wang, H. Huang, S. Chen, Y. Li, Q. Liu, Zhibo Han, Z. Guo, Zhongchao Han, Z. Li
Mesenchymal stem cell-derived extracellular vesicles attenuate radiation-induced lung injury via miR-214-3p
Antioxid. Redox Signal., 35 (2021), pp. 849-862, 10.1089/ars.2019.7965
View in ScopusGoogle Scholar
Levine and Kroemer, 2019
B. Levine, G. Kroemer
Biological functions of autophagy genes: a disease perspective
Cell, 176 (2019), pp. 11-42, 10.1016/j.cell.2018.09.048
View PDF
View articleView in ScopusGoogle Scholar
Li et al., 2023
Z. Li, Y. Liu, Y. Tian, Q. Li, W. Shi, J. Zhang, H. Zhang, Y. Tan, S. Yang, T. Yang, X. Huang, Y. Du
Human umbilical cord mesenchymal stem cell-derived exosomes improve ovarian function in natural aging by inhibiting apoptosis
Int. J. Mol. Med., 52 (2023), p. 94, 10.3892/ijmm.2023.5297
View PDF
View articleGoogle Scholar
Lian et al., 2010
Q. Lian, Yuelin Zhang, J. Zhang, H.K. Zhang, X. Wu, Yang Zhang, F.F.-Y. Lam, S. Kang, J.C. Xia, W.-H. Lai, K.-W. Au, Y.Y. Chow, C.-W. Siu, C.-N. Lee, H.-F. Tse
Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice
Circulation, 121 (2010), pp. 1113-1123, 10.1161/CIRCULATIONAHA.109.898312
View in ScopusGoogle Scholar
Liao et al., 2021
C.M. Liao, T. Luo, J. von der Ohe, B. de Juan Mora, R. Schmitt, R. Hass
Human MSC-derived exosomes reduce cellular senescence in renal epithelial cells
Int. J. Mol. Sci., 22 (2021), p. 13562, 10.3390/ijms222413562
View in ScopusGoogle Scholar
Lin et al., 2019
H. Lin, J. Sohn, H. Shen, M.T. Langhans, R.S. Tuan
Bone marrow mesenchymal stem cells: Aging and tissue engineering applications to enhance bone healing
Biomaterials, 203 (2019), pp. 96-110, 10.1016/j.biomaterials.2018.06.026
View PDF
View articleView in ScopusGoogle Scholar
Liu et al., 2021
A. Liu, D. Lin, H. Zhao, L. Chen, B. Cai, K. Lin, S.G. Shen
Optimized BMSC-derived osteoinductive exosomes immobilized in hierarchical scaffold via lyophilization for bone repair through Bmpr2/Acvr2b competitive receptor-activated Smad pathway
Biomaterials, 272 (2021), Article 120718, 10.1016/j.biomaterials.2021.120718
View PDF
View articleView in ScopusGoogle Scholar
Liu et al., 2022a
C. Liu, C. Wang, F. Yang, Y. Lu, P. Du, K. Hu, X. Yin, P. Zhao, G. Lu
The conditioned medium from mesenchymal stromal cells pretreated with proinflammatory cytokines promote fibroblasts migration and activation
PLoS One, 17 (2022), Article e0265049, 10.1371/journal.pone.0265049
View in ScopusGoogle Scholar
Liu et al., 2022b
Q. Liu, J. Zhang, Y. Tang, Y. Ma, Z. Xue, J. Wang
The effects of human umbilical cord mesenchymal stem cell transplantation on female fertility restoration in mice
Curr. Gene Ther., 22 (2022), pp. 319-330, 10.2174/1566523221666211014165341
View in ScopusGoogle Scholar
López-Otín et al., 2023
C. López-Otín, M.A. Blasco, L. Partridge, M. Serrano, G. Kroemer
Hallmarks of aging: an expanding universe
Cell, 186 (2023), pp. 243-278, 10.1016/j.cell.2022.11.001
View PDF
View articleView in ScopusGoogle Scholar
Lu et al., 2021
Y.-X. Lu, J.C. Regan, J. Eßer, L.F. Drews, T. Weinseis, J. Stinn, O. Hahn, R.A. Miller, S. Grönke, L. Partridge
A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing
Elife, 10 (2021), Article e62233, 10.7554/eLife.62233
View in ScopusGoogle Scholar
Luo et al., 2023
X. Luo, Y. Li, Z. Hua, X. Xue, X. Wang, M. Pang, C. Xiao, H. Zhao, A. Lyu, Y. Liu
Exosomes-mediated tumor metastasis through reshaping the tumor microenvironment and distant niche
J. Control. Release, 353 (2023), pp. 327-336, 10.1016/j.jconrel.2022.11.050
View PDF
View articleView in ScopusGoogle Scholar
Lv et al., 2021
M. Lv, S. Zhang, B. Jiang, S. Cao, Y. Dong, L. Cao, S. Guo
Adipose-derived stem cells regulate metabolic homeostasis and delay aging by promoting mitophagy
FASEB J., 35 (2021), Article e21709, 10.1096/fj.202100332R
View in ScopusGoogle Scholar
Mai et al., 2021
Z. Mai, H. Chen, Y. Ye, Z. Hu, W. Sun, L. Cui, X. Zhao
Translational and clinical applications of dental stem cell-derived exosomes
Front. Genet., 12 (2021), Article 750990, 10.3389/fgene.2021.750990
View in ScopusGoogle Scholar
Maqsood et al., 2020
M. Maqsood, M. Kang, X. Wu, J. Chen, L. Teng, L. Qiu
Adult mesenchymal stem cells and their exosomes: sources, characteristics, and application in regenerative medicine
Life Sci., 256 (2020), Article 118002, 10.1016/j.lfs.2020.118002
View PDF
View articleView in ScopusGoogle Scholar
Maremanda et al., 2019
K.P. Maremanda, I.K. Sundar, I. Rahman
Protective role of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in cigarette smoke-induced mitochondrial dysfunction in mice
Toxicol. Appl. Pharmacol., 385 (2019), Article 114788, 10.1016/j.taap.2019.114788
View PDF
View articleView in ScopusGoogle Scholar
Martinez-Miguel et al., 2021
V.E. Martinez-Miguel, C. Lujan, T. Espie-Caullet, D. Martinez-Martinez, S. Moore, C. Backes, S. Gonzalez, E.R. Galimov, A.E.X. Brown, M. Halic, K. Tomita, C. Rallis, T. von der Haar, F. Cabreiro, I. Bjedov
Increased fidelity of protein synthesis extends lifespan
Cell Metab., 33 (2021), pp. 2288-2300.e12, 10.1016/j.cmet.2021.08.017
View PDF
View articleView in ScopusGoogle Scholar
Martin-Montalvo et al., 2013
A. Martin-Montalvo, E.M. Mercken, S.J. Mitchell, H.H. Palacios, P.L. Mote, M. Scheibye-Knudsen, A.P. Gomes, T.M. Ward, R.K. Minor, M.-J. Blouin, M. Schwab, M. Pollak, Y. Zhang, Y. Yu, K.G. Becker, V.A. Bohr, D.K. Ingram, D.A. Sinclair, N.S. Wolf, S.R. Spindler, M. Bernier, R. de Cabo
Metformin improves healthspan and lifespan in mice
Nat. Commun., 4 (2013), p. 2192, 10.1038/ncomms3192
View in ScopusGoogle Scholar
Matsuoka et al., 2021
T. Matsuoka, K. Takanashi, K. Dan, K. Yamamoto, K. Tomobe, T. Shinozuka
Effects of mesenchymal stem cell-derived exosomes on oxidative stress responses in skin cells
Mol. Biol. Rep., 48 (2021), pp. 4527-4535, 10.1007/s11033-021-06473-z
View in ScopusGoogle Scholar
Merino et al., 2021
A. Merino, M.J. Hoogduijn, M. Molina-Molina, E.G. Arias-Salgado, S.S. Korevaar, C.C. Baan, A. Montes-Worboys
Membrane particles from mesenchymal stromal cells reduce the expression of fibrotic markers on pulmonary cells
PLoS One, 16 (2021), Article e0248415, 10.1371/journal.pone.0248415
View in ScopusGoogle Scholar
Mianehsaz et al., 2019
E. Mianehsaz, H.R. Mirzaei, M. Mahjoubin-Tehran, A. Rezaee, R. Sahebnasagh, M.H. Pourhanifeh, H. Mirzaei, M.R. Hamblin
Mesenchymal stem cell-derived exosomes: a new therapeutic approach to osteoarthritis?
Stem Cell Res Ther, 10 (2019), p. 340, 10.1186/s13287-019-1445-0
View in ScopusGoogle Scholar
Miller et al., 2020
H.A. Miller, E.S. Dean, S.D. Pletcher, S.F. Leiser
Cell non-autonomous regulation of health and longevity
Elife, 9 (2020), Article e62659, 10.7554/eLife.62659
Google Scholar
Motawea et al., 2020
S.M. Motawea, R.I. Noreldin, Y.M. Naguib
Potential therapeutic effects of endothelial cells trans-differentiated from Wharton’s Jelly-derived mesenchymal stem cells on altered vascular functions in aged diabetic rat model
Diabetol. Metab. Syndr., 12 (2020), p. 40, 10.1186/s13098-020-00546-y
View in ScopusGoogle Scholar
Nadon et al., 2017
N.L. Nadon, R. Strong, R.A. Miller, D.E. Harrison
NIA interventions testing program: investigating putative aging intervention agents in a genetically heterogeneous mouse model
EBioMedicine, 21 (2017), pp. 3-4, 10.1016/j.ebiom.2016.11.038
View PDF
View articleView in ScopusGoogle Scholar
Nguyen et al., 2024
N.-H.T. Nguyen, H.T. Phan, P.M. Le, L.-H.T. Nguyen, T.T. Do, T.-P.T. Phan, T. Van Le, T.M. Dang, C.-N.L. Phan, T.-L.T. Dang, N.H. Truong
Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial
Trials, 25 (2024), p. 309, 10.1186/s13063-024-08128-3
View in ScopusGoogle Scholar
P et al., 2019
P. P, D. Q, W. D, Chang J, W. C, D. M, L. J, K. J, N. Lj, R. Pd, S. G, Campisi J, Z. D, V. N
Systemic clearance of p16INK4a-positive senescent cells mitigates age-associated intervertebral disc degeneration
Aging Cell, 18 (3) (2019), Article e12927, 10.1111/acel.12927
Google Scholar
Partridge et al., 2020
L. Partridge, M. Fuentealba, B.K. Kennedy
The quest to slow ageing through drug discovery
Nat. Rev. Drug Discov., 19 (2020), pp. 513-532, 10.1038/s41573-020-0067-7
View in ScopusGoogle Scholar
Piao et al., 2022
L. Piao, Z. Huang, A. Inoue, M. Kuzuya, X.W. Cheng
Human umbilical cord-derived mesenchymal stromal cells ameliorate aging-associated skeletal muscle atrophy and dysfunction by modulating apoptosis and mitochondrial damage in SAMP10 mice
Stem Cell Res Ther, 13 (2022), p. 226, 10.1186/s13287-022-02895-z
View in ScopusGoogle Scholar
Psaraki et al., 2022
A. Psaraki, L. Ntari, C. Karakostas, D. Korrou-Karava, M.G. Roubelakis
Extracellular vesicles derived from mesenchymal stem/stromal cells: the regenerative impact in liver diseases
Hepatology, 75 (2022), pp. 1590-1603, 10.1002/hep.32129
View in ScopusGoogle Scholar
Qi et al., 2019
L. Qi, R. Wang, Q. Shi, M. Yuan, M. Jin, D. Li
Umbilical cord mesenchymal stem cell conditioned medium restored the expression of collagen II and aggrecan in nucleus pulposus mesenchymal stem cells exposed to high glucose
J. Bone Miner. Metab., 37 (2019), pp. 455-466, 10.1007/s00774-018-0953-9
View in ScopusGoogle Scholar
Qian et al., 2021
X. Qian, N. An, Y. Ren, C. Yang, X. Zhang, L. Li
Immunosuppressive effects of mesenchymal stem cells-derived exosomes
Stem Cell Rev. Rep., 17 (2021), pp. 411-427, 10.1007/s12015-020-10040-7
View in ScopusGoogle Scholar
Rash et al., 2025
B.G. Rash, K.N. Ramdas, N. Agafonova, E. Naioti, L. McClain-Moss, Z. Zainul, B. Varnado, K. Peterson, M. Brown, T. Leal, S. Kopcho, R. Carballosa, P. Patel, M. Brody, B. Herskowitz, A. Fuquay, S. Rodriguez, A.F. Jacobson, R. Leon, M. Pfeffer, J.B. Schwartzbard, J. Botbyl, A.A. Oliva, J.M. Hare
Allogeneic mesenchymal stem cell therapy with laromestrocel in mild Alzheimer’s disease: a randomized controlled phase 2a trial
Nat. Med. (2025), 10.1038/s41591-025-03559-0
Google Scholar
Schmeer et al., 2019
C. Schmeer, A. Kretz, D. Wengerodt, M. Stojiljkovic, O.W. Witte
Dissecting aging and senescence-current concepts and open lessons
Cells, 8 (2019), p. 1446, 10.3390/cells8111446
View in ScopusGoogle Scholar
Schulman et al., 2018
I.H. Schulman, W. Balkan, J.M. Hare
Mesenchymal stem cell therapy for aging frailty
Front Nutr, 5 (2018), p. 108, 10.3389/fnut.2018.00108
View in ScopusGoogle Scholar
Seale et al., 2022
K. Seale, S. Horvath, A. Teschendorff, N. Eynon, S. Voisin
Making sense of the ageing methylome
Nat. Rev. Genet., 23 (2022), pp. 585-605, 10.1038/s41576-022-00477-6
View in ScopusGoogle Scholar
Sha et al., 2021
S. Sha, X. Shen, Y. Cao, L. Qu
Mesenchymal stem cells-derived extracellular vesicles ameliorate Alzheimer’s disease in rat models via the microRNA-29c-3p/BACE1 axis and the Wnt/β-catenin pathway
Aging (Albany NY), 13 (2021), pp. 15285-15306, 10.18632/aging.203088
View in ScopusGoogle Scholar
Shetty et al., 2018
A.K. Shetty, M. Kodali, R. Upadhya, L.N. Madhu
Emerging anti-aging strategies – scientific basis and efficacy
Aging Dis., 9 (2018), pp. 1165-1184, 10.14336/AD.2018.1026
View in ScopusGoogle Scholar
Shi et al., 2021
L. Shi, Q. Han, Y. Hong, W. Li, G. Gong, J. Cui, M. Mao, X. Liang, B. Hu, X. Li, Q. Luo, Y. Zhang
Inhibition of miR-199a-5p rejuvenates aged mesenchymal stem cells derived from patients with idiopathic pulmonary fibrosis and improves their therapeutic efficacy in experimental pulmonary fibrosis
Stem Cell Res Ther, 12 (2021), p. 147, 10.1186/s13287-021-02215-x
Google Scholar
Siu et al., 2010
C.-W. Siu, S.-Y. Liao, Y. Liu, Q. Lian, H.-F. Tse
Stem cells for myocardial repair
Thromb. Haemost., 104 (2010), pp. 6-12, 10.1160/TH09-05-0336
View in ScopusGoogle Scholar
Spees et al., 2016
J.L. Spees, R.H. Lee, C.A. Gregory
Mechanisms of mesenchymal stem/stromal cell function
Stem Cell Res Ther, 7 (2016), p. 125, 10.1186/s13287-016-0363-7
View in ScopusGoogle Scholar
Su et al., 2019
T. Su, Yuzhong Xiao, Ye Xiao, Q. Guo, C. Li, Y. Huang, Q. Deng, J. Wen, F. Zhou, X.-H. Luo
Bone marrow mesenchymal stem cells-derived exosomal miR-29b-3p regulates aging-associated insulin resistance
ACS Nano, 13 (2019), pp. 2450-2462, 10.1021/acsnano.8b09375
View in ScopusGoogle Scholar
Sun et al., 2018
Z. Sun, Y. Ma, F. Chen, S. Wang, B. Chen, J. Shi
miR-133b and miR-199b knockdown attenuate TGF-β1-induced epithelial to mesenchymal transition and renal fibrosis by targeting SIRT1 in diabetic nephropathy
Eur. J. Pharmacol., 837 (2018), pp. 96-104, 10.1016/j.ejphar.2018.08.022
View PDF
View articleView in ScopusGoogle Scholar
Swer and Sharma, 2021
P.B. Swer, R. Sharma
ATP-dependent chromatin remodelers in ageing and age-related disorders
Biogerontology, 22 (2021), pp. 1-17, 10.1007/s10522-020-09899-3
Google Scholar
Tao et al., 2017
S.-C. Tao, T. Yuan, Y.-L. Zhang, W.-J. Yin, S.-C. Guo, C.-Q. Zhang
Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model
Theranostics, 7 (2017), pp. 180-195, 10.7150/thno.17133
View in ScopusGoogle Scholar
Tsakiri et al., 2013
E.N. Tsakiri, K.K. Iliaki, A. Höhn, S. Grimm, I.S. Papassideri, T. Grune, I.P. Trougakos
Diet-derived advanced glycation end products or lipofuscin disrupts proteostasis and reduces life span in Drosophila melanogaster
Free Radic. Biol. Med., 65 (2013), pp. 1155-1163, 10.1016/j.freeradbiomed.2013.08.186
View PDF
View articleView in ScopusGoogle Scholar
Uder et al., 2018
C. Uder, S. Brückner, S. Winkler, H.-M. Tautenhahn, B. Christ
Mammalian MSC from selected species: features and applications
Cytometry A, 93 (2018), pp. 32-49, 10.1002/cyto.a.23239
View in ScopusGoogle Scholar
Vijg and Dong, 2020
J. Vijg, X. Dong
Pathogenic mechanisms of somatic mutation and genome mosaicism in aging
Cell, 182 (2020), pp. 12-23, 10.1016/j.cell.2020.06.024
View PDF
View articleView in ScopusGoogle Scholar
Walberer et al., 2014
M. Walberer, S.U. Jantzen, H. Backes, M.A. Rueger, M.H. Keuters, B. Neumaier, M. Hoehn, G.R. Fink, R. Graf, M. Schroeter
In-vivo detection of inflammation and neurodegeneration in the chronic phase after permanent embolic stroke in rats
Brain Res., 1581 (2014), pp. 80-88, 10.1016/j.brainres.2014.05.030
View PDF
View articleView in ScopusGoogle Scholar
Wang et al., 2020
Lu Wang, Y. Lv, C. Li, G. Yang, B. Fu, Q. Peng, L. Jian, D. Hou, J. Wang, C. Zhao, P. Yang, K. Zhang, Lei Wang, Z. Wang, H. Wang, W. Xu
Transformable dual-inhibition system effectively suppresses renal cancer metastasis through blocking endothelial cells and cancer stem cells
Small, 16 (2020), Article e2004548, 10.1002/smll.202004548
Google Scholar
Wang et al., 2023
F. Wang, Y. Li, B. Wang, J. Li, Z. Peng
The safety and efficacy of mesenchymal stromal cells in ARDS: a meta-analysis of randomized controlled trials
Crit. Care, 27 (2023), p. 31, 10.1186/s13054-022-04287-4
View at publisher
Google Scholar
X et al., 2021
X. X, X. M, Y. H, W. L, L. X, R. J, W. S, Z. Rc
Mesenchymal stem cell-derived small extracellular vesicles mitigate oxidative stress-induced senescence in endothelial cells via regulation of miR-146a/Src
Signal Transduct. Target. Ther., 6 (1) (2021), Article 354, 10.1038/s41392-021-00765-3
View at publisherGoogle Scholar
Xia and Hou, 2018
W. Xia, M. Hou
Mesenchymal stem cells confer resistance to doxorubicin-induced cardiac senescence by inhibiting microRNA-34a
Oncol. Lett., 15 (2018), pp. 10037-10046, 10.3892/ol.2018.8438
View at publisherView in ScopusGoogle Scholar
Xiong et al., 2021
Yanlian Xiong, Yanlei Xiong, H. Zhang, Y. Zhao, K. Han, J. Zhang, D. Zhao, Z. Yu, Z. Geng, L. Wang, Y. Wang, X. Luan
hPMSCs-derived exosomal miRNA-21 protects against aging-related oxidative damage of CD4+ T cells by targeting the PTEN/PI3K-Nrf2 Axis
Front. Immunol., 12 (2021), Article 780897, 10.3389/fimmu.2021.780897
View at publisherView in ScopusGoogle Scholar
Y et al., 2016
Z. Y, Y. Z, J. D, Liang X, L. S, Z. Z, Y. W, Li X, C. Sm, C. Yh, L. Y, C. Y, H. S, X. A, T. Hf, L. Q
iPSC-MSCs with high intrinsic MIRO1 and sensitivity to TNF-α yield efficacious mitochondrial transfer to rescue anthracycline-induced cardiomyopathy
Stem Cell Rep., 7 (4) (2016), pp. 749-763, 10.1016/j.stemcr.2016.08.009
Google Scholar
Yin et al., 2022
B. Yin, J. Ni, C.E. Witherel, M. Yang, J.A. Burdick, C. Wen, S.H.D. Wong
Harnessing tissue-derived extracellular vesicles for osteoarthritis theranostics
Theranostics, 12 (2022), pp. 207-231, 10.7150/thno.62708
View in ScopusGoogle Scholar
Yu et al., 2021
H. Yu, Y. Hua, Y. He, Y. Wang, X. Hu, S. Chen, J. Liu, J. Yang, H. Li
Sustained release of MiR-217 inhibitor by nanoparticles facilitates MSC-mediated attenuation of neointimal hyperplasia after vascular injury
Front Cardiovasc Med, 8 (2021), Article 739107, 10.3389/fcvm.2021.739107
View in ScopusGoogle Scholar
Zhai et al., 2022
Q.-Y. Zhai, Y.-Q. Ren, Q.-S. Ni, Z.-H. Song, K.-L. Ge, Y.-L. Guo
Transplantation of human umbilical cord mesenchymal stem cells-derived neural stem cells pretreated with neuregulin1β ameliorate cerebral ischemic reperfusion injury in rats
Biomolecules, 12 (2022), p. 428, 10.3390/biom12030428
View in ScopusGoogle Scholar
Zhang et al., 2018
S. Zhang, S.J. Chuah, R.C. Lai, J.H.P. Hui, S.K. Lim, W.S. Toh
MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity
Biomaterials, 156 (2018), pp. 16-27, 10.1016/j.biomaterials.2017.11.028
View PDF
View articleView in ScopusGoogle Scholar
Zhang et al., 2019
S. Zhang, K.Y.W. Teo, S.J. Chuah, R.C. Lai, S.K. Lim, W.S. Toh
MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis
Biomaterials, 200 (2019), pp. 35-47, 10.1016/j.biomaterials.2019.02.006
View PDF
View articleView in ScopusGoogle Scholar
Zhang et al., 2023
X. Zhang, T. Liu, X. Hou, Z. Zhou, F. Zhang, H. Ma, X. Wu, J. Jiang
Exosomes secreted by mesenchymal stem cells delay brain aging by upregulating SIRT1 expression
Sci. Rep., 13 (2023), p. 13213, 10.1038/s41598-023-40543-5
View in ScopusGoogle Scholar
Zhou et al., 2021
T. Zhou, Z. Yuan, J. Weng, D. Pei, X. Du, C. He, P. Lai
Challenges and advances in clinical applications of mesenchymal stromal cells
J. Hematol. Oncol., 14 (2021), p. 24, 10.1186/s13045-021-01037-x
Google Scholar
Zhu et al., 2024
Y. Zhu, C. Huang, L. Zheng, Q. Li, J. Ge, S. Geng, M. Zhai, X. Chen, H. Yuan, Yang Li, W. Jia, K. Sun, Yan Li, T. Ye, Z. Zhao, H. Liu, Z. Liu, H. Jiang
Safety and efficacy of umbilical cord tissue-derived mesenchymal stem cells in the treatment of patients with aging frailty: a phase I/II randomized, double-blind, placebo-controlled study
Stem Cell Res Ther, 15 (2024), p. 122, 10.1186/s13287-024-03707-2
Google Scholar
Zuo et al., 2019
R. Zuo, M. Liu, Y. Wang, J. Li, W. Wang, J. Wu, C. Sun, B. Li, Z. Wang, W. Lan, C. Zhang, C. Shi, Y. Zhou
BM-MSC-derived exosomes alleviate radiation-induced bone loss by restoring the function of recipient BM-MSCs and activating Wnt/β-catenin signaling