{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:26:48Z","timestamp":1786966008236,"version":"build-2736575974"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:p>Mesenchymal stem cells (MSCs) are widely investigated for regenerative medicine, tissue repair, immunomodulation, and selected cancer-related applications because of their multilineage differentiation potential, paracrine activity, immunoregulatory properties, and capacity to home to sites of injury. However, the therapeutic potential of MSCs depends not only on their tissue source or surface-marker expression but also on their functional state. MSC senescence is not a single phenotypic alteration; rather, it reflects the combined effects of persistent DNA damage response activation, disruption of mitochondrial and metabolic homeostasis, remodeling of epigenetic and secretory networks, and loss of proteostasis. Collectively, these changes drive MSCs toward reduced proliferative capacity, dysregulated paracrine signaling, impaired immunomodulatory activity, and diminished tissue-repair potential, thereby compromising cell-product potency and batch-to-batch consistency. This review summarizes the molecular mechanisms underlying MSC senescence, its source-specific functional consequences, and emerging rejuvenation strategies, with an emphasis on MSC quality control, potency assessment, and clinical translation.<\/jats:p>","DOI":"10.3389\/fragi.2026.1929624","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:00:47Z","timestamp":1786964447000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mesenchymal stem cell senescence as a potency brake: causes, consequences, and cures"],"prefix":"10.3389","volume":"7","author":[{"given":"Sen","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Immunology, Yan\u2019an Medical College, Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Immunology, Yan\u2019an Medical College, Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Immunology, Yan\u2019an Medical College, Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Yan\u2019an Medical College, Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.reth.2023.03.006","article-title":"Reconstitution and post-thaw storage of cryopreserved human mesenchymal stromal cells: pitfalls and optimizations for clinically compatible formulants","volume":"23","author":"Aabling","year":"2023","journal-title":"Regen. Ther."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1016\/j.jcyt.2024.05.007","article-title":"International society for cell and gene therapy clinical translation committee recommendations on mesenchymal stromal cells in graft-versus-host disease: easy manufacturing is faced with standardizing and commercialization challenges","volume":"26","author":"Alsultan","year":"2024","journal-title":"Cytotherapy"},{"key":"B3","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1186\/s12951-024-02509-1","article-title":"Extracellular vesicles from senescent mesenchymal stromal cells are defective and cannot prevent osteoarthritis","volume":"22","author":"Boulestreau","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.jcyt.2024.11.014","article-title":"Role of mesenchymal stromal cell secretome on recovery from cellular senescence: an overview","volume":"27","author":"Brito","year":"2025","journal-title":"Cytotherapy"},{"key":"B5","doi-asserted-by":"publisher","first-page":"650431","DOI":"10.3389\/fcell.2021.650431","article-title":"Non-coding RNAs steering the senescence-related progress, properties, and application of mesenchymal stem cells","volume":"9","author":"Cai","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1400347","DOI":"10.3389\/fcell.2024.1400347","article-title":"The issue of heterogeneity of MSC-Based advanced therapy medicinal products-a review","volume":"12","author":"\u010cesnik","year":"2024","journal-title":"Front. Cell Dev. Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s00018-023-04975-6","article-title":"Silencing circSERPINE2 restrains mesenchymal stem cell senescence via the YBX3\/PCNA\/p21 axis","volume":"80","author":"Chen","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41368-024-00309-9","article-title":"Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure","volume":"16","author":"Chen","year":"2024","journal-title":"Int. J. Oral Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.jare.2024.06.019","article-title":"WTAP\/YTHDF1-mediated m6A modification amplifies IFN-\u03b3-induced immunosuppressive properties of human MSCs","volume":"71","author":"Chen","year":"2025","journal-title":"J. Adv. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3324","DOI":"10.3390\/cells11203324","article-title":"Paracrine senescence of mesenchymal stromal cells involves inflammatory cytokines and the NF-\u03baB pathway","volume":"11","author":"Chou","year":"2022","journal-title":"Cells"},{"key":"B11","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s13287-024-03757-6","article-title":"Possibilities and efficiency of MSC co-transfection for gene therapy","volume":"15","author":"Christoffers","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.bioactmat.2023.04.007","article-title":"Novel neutrophil extracellular trap-related mechanisms in diabetic wounds inspire a promising treatment strategy with hypoxia-challenged small extracellular vesicles","volume":"27","author":"Chu","year":"2023","journal-title":"Bioact. Mater."},{"key":"B13","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s13287-024-03725-0","article-title":"A GMP-Compliant manufacturing method for Wharton's jelly-derived mesenchymal stromal cells","volume":"15","author":"Chu","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"B14","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/s40778-022-00212-1","article-title":"Impact of cryopreservation and freeze-thawing on therapeutic properties of mesenchymal stromal\/stem cells and other common cellular therapeutics","volume":"8","author":"Cottle","year":"2022","journal-title":"Curr. Stem Cell Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1016\/j.jcyt.2025.06.005","article-title":"Defining minimal criteria for peer-reviewed reporting of mesenchymal stromal cell clinical trials for autoimmune diseases","volume":"27","author":"Davies","year":"2025","journal-title":"Cytotherapy"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.stem.2021.01.010","article-title":"Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging","volume":"28","author":"Deng","year":"2021","journal-title":"Cell Stem Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1002\/elsc.202100097","article-title":"Physiologic isolation and expansion of human mesenchymal stem\/stromal cells for manufacturing of cell-based therapy products","volume":"22","author":"Egger","year":"2022","journal-title":"Eng. Life Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"111829","DOI":"10.1016\/j.exger.2022.111829","article-title":"Parkin-mediated mitophagy protects against TNF-\u03b1-induced stress in bone marrow mesenchymal stem cells","volume":"164","author":"Fan","year":"2022","journal-title":"Exp. Gerontol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"8390","DOI":"10.3390\/ijms25158390","article-title":"Senescence in adipose-derived stem cells: biological mechanisms and therapeutic challenges","volume":"25","author":"Foti","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"147","DOI":"10.3109\/14653249.2011.623691","article-title":"Cryopreserved mesenchymal stromal cells display impaired immunosuppressive properties as a result of heat-shock response and impaired interferon-\u03b3 licensing","volume":"14","author":"Fran\u00e7ois","year":"2012","journal-title":"Cytotherapy"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3960\/jslrt.16019","article-title":"Isolation of mesenchymal stromal\/stem cells from cryopreserved umbilical cord blood cells","volume":"57","author":"Fujii","year":"2017","journal-title":"J. Clin. Exp. Hematop."},{"key":"B22","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s12979-023-00378-0","article-title":"Obesity drives adipose-derived stem cells into a senescent and dysfunctional phenotype associated with P38MAPK\/NF-KB axis","volume":"20","author":"Grun","year":"2023","journal-title":"Immun. Ageing"},{"key":"B23","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41392-022-00932-0","article-title":"The secretion profile of mesenchymal stem cells and potential applications in treating human diseases","volume":"7","author":"Han","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"B24","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/s41392-025-02313-9","article-title":"Mesenchymal stem cells in treating human diseases: molecular mechanisms and clinical studies","volume":"10","author":"Han","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"B25","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1093\/procel\/pwac037","article-title":"4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis","volume":"14","author":"He","year":"2023","journal-title":"Protein Cell"},{"key":"B26","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1182\/bloodadvances.2022007033","article-title":"p16INK4A-dependent senescence in the bone marrow niche drives age-related metabolic changes of hematopoietic progenitors","volume":"7","author":"Hellmich","year":"2023","journal-title":"Blood Adv."},{"key":"B27","doi-asserted-by":"publisher","first-page":"11420","DOI":"10.1038\/s41467-025-66281-y","article-title":"TRIM37-PARP1-TET1 axis maintains stemness and prevents osteoporosis by inhibiting DNMT1 alternative splicing via 5hmC regulation","volume":"16","author":"Ho","year":"2025","journal-title":"Nat. Commun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1329218","DOI":"10.3389\/fcell.2024.1329218","article-title":"Superior migration ability of umbilical cord-derived mesenchymal stromal cells (MSCs) toward activated lymphocytes in comparison with those of bone marrow and adipose-derived MSCs","volume":"12","author":"Hori","year":"2024","journal-title":"Front. Cell Dev. Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s13577-025-01213-y","article-title":"The influence of cell source on the senescence of human mesenchymal stem\/stromal cells","volume":"38","author":"Hoseini","year":"2025","journal-title":"Hum. Cell"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1016\/j.ymthe.2024.05.018","article-title":"Carbon monoxide-induced autophagy enhances human mesenchymal stromal cell function via paracrine actions in murine polymicrobial sepsis","volume":"32","author":"Hwang","year":"2024","journal-title":"Mol. Ther."},{"key":"B31","doi-asserted-by":"publisher","first-page":"12533","DOI":"10.3390\/ijms252312533","article-title":"Partial reprogramming exerts a rejuvenating effect on human mesenchymal stem cells that underwent replicative senescence in culture","volume":"25","author":"Ivanova","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"10046","DOI":"10.1038\/s41467-024-54338-3","article-title":"Disorganized chromatin hierarchy and stem cell aging in a Male patient of atypical laminopathy-based progeria mandibuloacral dysplasia type A","volume":"15","author":"Jin","year":"2024","journal-title":"Nat. Commun."},{"key":"B33","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/s12964-024-01705-8","article-title":"Podoplanin depletion in tonsil-derived mesenchymal stem cells induces cellular senescence via regulation of the p16(Ink4a)\/Rb pathway","volume":"22","author":"Kim","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"B34","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s13258-022-01297-y","article-title":"Small RNA sequencing of small extracellular vesicles secreted by umbilical cord mesenchymal stem cells following replicative senescence","volume":"45","author":"Kim","year":"2023","journal-title":"Genes Genom."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e13111","DOI":"10.1111\/acel.13111","article-title":"Melatonin suppresses senescence-derived mitochondrial dysfunction in mesenchymal stem cells via the HSPA1L-mitophagy pathway","volume":"19","author":"Lee","year":"2020","journal-title":"Aging Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"151331","DOI":"10.1016\/j.ejcb.2023.151331","article-title":"Stress-induced senescence in mesenchymal stem cells: triggers, hallmarks, and current rejuvenation approaches","volume":"102","author":"Lee","year":"2023","journal-title":"Eur. J. Cell Biol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e2100964","DOI":"10.1002\/advs.202100964","article-title":"Rejuvenation of senescent bone marrow mesenchymal stromal cells by pulsed triboelectric stimulation","volume":"8","author":"Li","year":"2021","journal-title":"Adv. Sci. (Weinh.)"},{"key":"B38","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1186\/s13287-023-03587-y","article-title":"The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy","volume":"14","author":"Li","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"B39","doi-asserted-by":"publisher","first-page":"111868","DOI":"10.1016\/j.mad.2023.111868","article-title":"Aging-related decrease of histone methyltransferase SUV39H1 in adipose-derived stem cells enhanced SASP","volume":"215","author":"Li","year":"2023","journal-title":"Mech. Ageing Dev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"bio060117","DOI":"10.1242\/bio.060117","article-title":"MiR-145-5p overexpression rejuvenates aged adipose stem cells and accelerates wound healing","volume":"13","author":"Li","year":"2024","journal-title":"Biol. Open"},{"key":"B41","doi-asserted-by":"publisher","first-page":"31291","DOI":"10.1038\/s41598-024-82614-1","article-title":"Curcumin liposomes alleviate senescence of bone marrow mesenchymal stem cells by activating mitophagy","volume":"14","author":"Li","year":"2024","journal-title":"Sci. Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"41354","DOI":"10.1038\/s41598-025-25240-9","article-title":"Resveratrol delays senescence of human dental pulp stem cells via activating the SIRT1-mitochondrial autophagy","volume":"15","author":"Li","year":"2025","journal-title":"Sci. Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"106788","DOI":"10.1016\/j.phrs.2023.106788","article-title":"S-sulfhydration of SIRT3 combats BMSC senescence and ameliorates osteoporosis via stabilizing heterochromatic and mitochondrial homeostasis","volume":"192","author":"Liu","year":"2023","journal-title":"Pharmacol. Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1186\/s13287-024-03866-2","article-title":"Senescent lung-resident mesenchymal stem cells drive pulmonary fibrogenesis through FGF-4\/FOXM1 axis","volume":"15","author":"Liu","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"B45","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/s41419-025-08094-x","article-title":"Understanding the molecular basis of mesenchymal stem cell stemness: implications for clinical applications","volume":"16","author":"Liu","year":"2025","journal-title":"Cell Death Dis."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e2210745120","DOI":"10.1073\/pnas.2210745120","article-title":"Loss of regulation of protein synthesis and turnover underpins an attenuated stress response in senescent human mesenchymal stem cells","volume":"120","author":"Llewellyn","year":"2023","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e2300381","DOI":"10.1002\/biot.202300381","article-title":"Identification of critical process parameters for expansion of clinical grade human Wharton's jelly-derived mesenchymal stromal cells in stirred-tank bioreactors","volume":"19","author":"L\u00f3pez-Fern\u00e1ndez","year":"2024","journal-title":"Biotechnol. J."},{"key":"B48","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41413-024-00351-7","article-title":"Rejuvenation of BMSCs senescence by pharmacological enhancement of TFEB-Mediated autophagy alleviates aged-related bone loss and extends lifespan in middle aged mice","volume":"12","author":"Luo","year":"2024","journal-title":"Bone Res."},{"key":"B49","doi-asserted-by":"publisher","first-page":"107765","DOI":"10.1016\/j.biotechadv.2021.107765","article-title":"Quality by design to define critical process parameters for mesenchymal stem cell expansion","volume":"50","author":"Maillot","year":"2021","journal-title":"Biotechnol. Adv."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1267550","DOI":"10.3389\/fimmu.2023.1267550","article-title":"Age-related changes in human bone marrow mesenchymal stromal cells: morphology, gene expression profile, immunomodulatory activity and miRNA expression","volume":"14","author":"Massaro","year":"2023","journal-title":"Front. Immunol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s13287-021-02222-y","article-title":"Human umbilical cord-derived mesenchymal stem\/stromal cells: a promising candidate for the development of advanced therapy medicinal products","volume":"12","author":"Mebarki","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"B52","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1186\/s13287-025-04361-y","article-title":"Pooling umbilical cord-mesenchymal stromal cells derived from selected multiple donors reduces donor-dependent variability and improves their immunomodulatory properties","volume":"16","author":"Mebarki","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"B53","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41556-022-01053-0","article-title":"Stromal niche inflammation mediated by IL-1 signalling is a targetable driver of haematopoietic ageing","volume":"25","author":"Mitchell","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"9636897211039441","DOI":"10.1177\/09636897211039441","article-title":"Comparative bioactivity analysis for off-the-shelf and culture-rescued umbilical cord-derived mesenchymal stem\/stromal cells in a xeno- and serum-free culture system","volume":"30","author":"Nguyen","year":"2021","journal-title":"Cell Transpl."},{"key":"B55","doi-asserted-by":"publisher","first-page":"870324","DOI":"10.3389\/fbioe.2022.870324","article-title":"Inflammatory microenvironment accelerates bone marrow mesenchymal stem cell aging","volume":"10","author":"Peng","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1186\/s12951-024-02818-5","article-title":"Young small extracellular vesicles rejuvenate replicative senescence by remodeling Drp1 translocation-mediated mitochondrial dynamics","volume":"22","author":"Peng","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"115679","DOI":"10.1016\/j.bone.2020.115679","article-title":"MicroRNAs are critical regulators of senescence and aging in mesenchymal stem cells","volume":"142","author":"Potter","year":"2021","journal-title":"Bone"},{"key":"B58","doi-asserted-by":"publisher","first-page":"120752","DOI":"10.1016\/j.biomaterials.2021.120752","article-title":"Heterospheroid formation improves therapeutic efficacy of mesenchymal stem cells in murine colitis through immunomodulation and epithelial regeneration","volume":"271","author":"Regmi","year":"2021","journal-title":"Biomaterials"},{"key":"B59","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1186\/s13287-021-02388-5","article-title":"The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients","volume":"12","author":"Ren","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"B60","doi-asserted-by":"publisher","first-page":"972095","DOI":"10.3389\/fimmu.2022.972095","article-title":"Putative critical quality attribute matrix identifies mesenchymal stromal cells with potent immunomodulatory and angiogenic \u201cfitness\u201d ranges in response to culture process parameters","volume":"13","author":"Robb","year":"2022","journal-title":"Front. Immunol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.jcyt.2023.09.001","article-title":"Failure to launch commercially-approved mesenchymal stromal cell therapies: what\u2019s the path forward? Proceedings of the International Society for Cell & Gene Therapy (ISCT) Annual Meeting Roundtable held in May 2023, Palais des Congr\u00e8s de Paris, organized by the ISCT MSC Scientific Committee","volume":"26","author":"Robb","year":"2024","journal-title":"Cytotherapy"},{"key":"B62","doi-asserted-by":"publisher","first-page":"9379","DOI":"10.3390\/ijms24119379","article-title":"Potency assays for mesenchymal stromal cell secretome-based products for tissue regeneration","volume":"24","author":"Sagaradze","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.jcyt.2022.08.005","article-title":"Adipose-derived stem cells applied in skin diseases, wound healing and skin defects: a review","volume":"25","author":"Schneider","year":"2023","journal-title":"Cytotherapy"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1111\/jcmm.17201","article-title":"Influence of age on stem cells depends on the sex of the bone marrow donor","volume":"26","author":"Selle","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"B65","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.freeradbiomed.2024.07.040","article-title":"ALDH2 regulates mesenchymal stem cell senescence via modulation of mitochondrial homeostasis","volume":"223","author":"Shen","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"B66","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s13287-021-02215-x","article-title":"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","volume":"12","author":"Shi","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"B67","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1007\/s12015-024-10812-5","article-title":"Automated manufacturing processes and platforms for large-scale production of clinical-grade mesenchymal stem\/stromal cells","volume":"21","author":"Strecanska","year":"2025","journal-title":"Stem Cell Rev. Rep."},{"key":"B68","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1016\/j.gendis.2022.10.030","article-title":"Epigenetic regulation of mesenchymal stem cell aging through histone modifications","volume":"10","author":"Sun","year":"2023","journal-title":"Genes Dis."},{"key":"B69","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1007\/s11357-023-00829-y","article-title":"Deconstructing heterogeneity of replicative senescence in human mesenchymal stem cells at single cell resolution","volume":"46","author":"Taherian Fard","year":"2024","journal-title":"GeroScience"},{"key":"B70","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1186\/s12903-025-05938-y","article-title":"High glucose induces senescence in synovial mesenchymal stem cells through mitochondrial dysfunction","volume":"25","author":"Tan","year":"2025","journal-title":"BMC Oral Health"},{"key":"B71","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1186\/s13287-024-03923-w","article-title":"Metabolic modulation to improve MSC expansion and therapeutic potential for articular cartilage repair","volume":"15","author":"Tee","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"B72","doi-asserted-by":"publisher","first-page":"5883","DOI":"10.1038\/s41467-022-32915-8","article-title":"Vitamin C epigenetically controls osteogenesis and bone mineralization","volume":"13","author":"Thaler","year":"2022","journal-title":"Nat. Commun."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1093\/stmcls\/sxad060","article-title":"Mesenchymal stromal cell secretome is affected by tissue source and donor age","volume":"41","author":"Turlo","year":"2023","journal-title":"Stem Cells"},{"key":"B74","doi-asserted-by":"publisher","first-page":"e0347781","DOI":"10.1371\/journal.pone.0347781","article-title":"Melatonin and coenzyme Q10 mitigate senescence in human adipose-derived mesenchymal stem cells by restoring mitophagy and mitochondrial proteostasis","volume":"21","author":"Vikraman","year":"2026","journal-title":"PLoS One"},{"key":"B75","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1016\/j.stem.2025.05.008","article-title":"Hallmarks of MSCs: key quality attributes for pharmacology and clinical use","volume":"32","author":"Viswanathan","year":"2025","journal-title":"Cell Stem Cell"},{"key":"B76","doi-asserted-by":"publisher","first-page":"254","DOI":"10.3390\/antiox10020254","article-title":"Exogenous NAD+ postpones the D-Gal-induced senescence of bone marrow-derived mesenchymal stem cells via Sirt1 signaling","volume":"10","author":"Wang","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B77","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.omtn.2021.08.013","article-title":"Effects of long-term culture on the biological characteristics and RNA profiles of human bone-marrow-derived mesenchymal stem cells","volume":"26","author":"Wang","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B78","doi-asserted-by":"publisher","first-page":"14739","DOI":"10.3390\/ijms232314739","article-title":"Nicotinamide mononucleotide supplementation improves mitochondrial dysfunction and rescues cellular senescence by NAD+\/Sirt3 pathway in mesenchymal stem cells","volume":"23","author":"Wang","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/j.stem.2022.10.001","article-title":"Reciprocal regulation of mesenchymal stem cells and immune responses","volume":"29","author":"Wang","year":"2022","journal-title":"Cell Stem Cell"},{"key":"B80","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1186\/s13287-023-03514-1","article-title":"Efficient expansion and delayed senescence of hUC-MSCs by microcarrier-bioreactor system","volume":"14","author":"Wang","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"B81","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s12015-022-10425-w","article-title":"PBX1-SIRT1 positive feedback loop attenuates ROS-Mediated HF-MSC senescence and apoptosis","volume":"19","author":"Wang","year":"2023","journal-title":"Stem Cell Rev. Rep."},{"key":"B82","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1021\/acsptsci.4c00284","article-title":"Emerging landscape of mesenchymal stem cell senescence mechanisms and implications on therapeutic strategies","volume":"7","author":"Wang","year":"2024","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"B83","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1186\/s13287-025-04422-2","article-title":"Short-term DMOG treatment rejuvenates senescent mesenchymal stem cells by enhancing mitochondrial function and mitophagy through the HIF-1\u03b1\/BNIP3 pathway","volume":"16","author":"Wen","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"B84","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1093\/stcltm\/szac004","article-title":"Mesenchymal stem\/stromal cell senescence: Hallmarks, mechanisms, and combating strategies","volume":"11","author":"Weng","year":"2022","journal-title":"Stem Cells Transl. Med."},{"key":"B85","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1186\/s13287-023-03604-0","article-title":"Umbilical cord mesenchymal stromal cells in serum-free defined medium display an improved safety profile","volume":"14","author":"Wu","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"B86","doi-asserted-by":"publisher","first-page":"609186","DOI":"10.3389\/fendo.2020.609186","article-title":"The p53\/miR-145a axis promotes cellular senescence and inhibits osteogenic differentiation by targeting cbfb in mesenchymal stem cells","volume":"11","author":"Xia","year":"2020","journal-title":"Front. Endocrinol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1093\/stcltm\/szad005","article-title":"A novel approach for determining the critical quality attributes of mesenchymal stem cells by specifying cell population with replication potential","volume":"12","author":"Yamamoto","year":"2023","journal-title":"Stem Cells Transl. Med."},{"key":"B88","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s13287-021-02194-z","article-title":"The role and mechanism of mitochondrial functions and energy metabolism in the function regulation of the mesenchymal stem cells","volume":"12","author":"Yan","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"B89","doi-asserted-by":"publisher","first-page":"998666","DOI":"10.3389\/fcell.2023.998666","article-title":"A passage-dependent network for estimating the in vitro senescence of mesenchymal stromal\/stem cells using microarray, bulk and single cell RNA sequencing","volume":"11","author":"Yang","year":"2023","journal-title":"Front. Cell Dev. Biol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s13287-022-02797-0","article-title":"Ascorbic acid 2-glucoside preconditioning enhances the ability of bone marrow mesenchymal stem cells in promoting wound healing","volume":"13","author":"Yi","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1038\/s41598-020-79831-9","article-title":"Multi-pronged approach to human mesenchymal stromal cells senescence quantification with a focus on label-free methods","volume":"11","author":"Zhai","year":"2021","journal-title":"Sci. Rep."},{"key":"B92","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/j.stemcr.2021.01.021","article-title":"Age-related changes in the inflammatory status of human mesenchymal stem cells: implications for cell therapy","volume":"16","author":"Zhang","year":"2021","journal-title":"Stem Cell Rep."},{"key":"B93","doi-asserted-by":"publisher","first-page":"112062","DOI":"10.1016\/j.exger.2022.112062","article-title":"Secretion of IL-6 and IL-8 in the senescence of bone marrow mesenchymal stem cells is regulated by autophagy via FoxO3a","volume":"172","author":"Zheng","year":"2023","journal-title":"Exp. Gerontol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1007\/s11626-021-00605-2","article-title":"Protective effect of MitoQ on oxidative stress-mediated senescence of canine bone marrow mesenchymal stem cells via activation of the Nrf2\/ARE pathway","volume":"57","author":"Zhong","year":"2021","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"B95","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13045-021-01037-x","article-title":"Challenges and advances in clinical applications of mesenchymal stromal cells","volume":"14","author":"Zhou","year":"2021","journal-title":"J. Hematol. Oncol."}],"container-title":["Frontiers in Aging"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2026.1929624\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:00:48Z","timestamp":1786964448000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2026.1929624\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":95,"alternative-id":["10.3389\/fragi.2026.1929624"],"URL":"https:\/\/doi.org\/10.3389\/fragi.2026.1929624","relation":{},"ISSN":["2673-6217"],"issn-type":[{"value":"2673-6217","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"article-number":"1929624"}}