{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:42:59Z","timestamp":1787636579156,"version":"build-2736575974"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"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. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Keloids and hypertrophic scars are pathological wound healing responses characterized by excessive scar tissue formation, presenting significant challenges to both patients and healthcare systems globally. Existing evidence demonstrates that mesenchymal stem cell\u2013derived extracellular vesicles (MSC-EVs) can attenuate collagen deposition and contraction in scar tissue; however, their application in the treatment of hypertrophic scars and keloids remains largely at the preclinical stage. This systematic review aims to critically assess preclinical studies on the therapeutic efficacy of MSC-EVs in the management of keloids and hypertrophic scars. The review synthesizes findings from controlled and interventional studies, focusing on the use of MSC-EVs in animal models of these scars and their application in human subjects with raised scars following skin injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 15 studies involving 253 animals were identified through a comprehensive search of the PubMed, Cochrane, Embase, MEDLINE Complete, Web of Science, CNKI, and Wanfang databases, covering the period from their inception to August 29, 2025. The aim was to evaluate the effects of MSC-EV therapy on keloids and hypertrophic scars through a meta-analysis of the standardized mean difference (SMD) in preclinical animal models. Meta-analyses were conducted using Stata 18 software.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Meta-analysis indicated that compared with the control group, MSC-Exos treatment group can significantly reduce. The dimensions of hypertrophic scars and keloids [(SMD) \u22122.78, 95% confidence interval (CI) \u22123.88\u20131.69)]. Also attenuate other outcomes, such as Collagen Type I [SMD = \u22124.39, 95%CI: \u22125.96\u20132.81], Collagen Type III [SMD = \u22125.19, 95%CI: \u22126.93\u20133.44], migration and proliferation of skin fibroblasts, and the expression of Transforming Growth Factor-\u03b21 (TGF-\u03b21) and \u03b1-smooth muscle actin (\u03b1-SMA) in scar tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The meta-analysis supports the therapeutic potential of MSC-EVs in the treatment of keloids and hypertrophic scars, as demonstrated in preclinical animal models. MSC-EV therapy has been shown to downregulate the dimensions of hypertrophic scars and keloids, inhibit collagen deposition, and reduce migration and proliferation of skin fibroblasts. Additionally, MSC-EVs suppress the expression of TGF-\u03b21 and \u03b1-SMA in scar tissue. These findings highlight MSC-EVs as a promising therapeutic approach for managing keloids and hypertrophic scars.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1739106","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T06:42:54Z","timestamp":1769582574000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Therapeutic value of mesenchymal stem cell-derived extracellular vesicles in hypertrophic and keloid scars: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"14","author":[{"given":"Tianhui","family":"Zhai","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery, Chengde Central Hospital, Chengde Medical College","place":["Chengde, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqi","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengchao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Nuclear Industry Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakun","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Chengde Central Hospital, Chengde Medical College","place":["Chengde, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Chengde Central Hospital","place":["Chengde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiqiang","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Chengde Central Hospital","place":["Chengde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3241","DOI":"10.1007\/s00018-014-1612-5","article-title":"Animal models in burn research","volume":"71","author":"Abdullahi","year":"2014","journal-title":"Cell Mol. Life Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1016\/j.drudis.2014.04.011","article-title":"Is nanotechnology a boon for oral drug delivery?","volume":"19","author":"Agrawal","year":"2014","journal-title":"Drug Discov. Today"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.3390\/pharmaceutics14112463","article-title":"Precision nanotoxicology in drug development: current trends and challenges in safety and toxicity implications of customized multifunctional nanocarriers for drug-delivery applications","volume":"14","author":"Ahmad","year":"2022","journal-title":"Pharmaceutics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s12931-018-0802-3","article-title":"Therapeutic effects of adipose-tissue-derived mesenchymal stromal cells and their extracellular vesicles in experimental silicosis","volume":"19","author":"Bandeira","year":"2018","journal-title":"Respir. Res."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051163","article-title":"Mesenchymal and induced pluripotent stem cells-derived extracellular vesicles: the new frontier for regenerative medicine?","volume":"9","author":"Barreca","year":"2020","journal-title":"Cells"},{"key":"B6","doi-asserted-by":"publisher","first-page":"283","DOI":"10.3892\/ijmm_00000231","article-title":"Keloids: current concepts of pathogenesis (review)","volume":"24","author":"Bran","year":"2009","journal-title":"Int. J. Mol. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1080\/13696998.2023.2232256","article-title":"Chronic wound prevalence and the associated cost of treatment in medicare beneficiaries: changes between 2014 and 2019","volume":"26","author":"Carter","year":"2023","journal-title":"J. Med. Econ."},{"key":"B8","doi-asserted-by":"publisher","first-page":"146","DOI":"10.3389\/fbioe.2020.00146","article-title":"Extracellular vesicles derived from mesenchymal stem cells (MSC) in regenerative medicine: applications in skin wound healing","volume":"8","author":"Casado-D\u00edaz","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"109733","DOI":"10.1016\/j.abb.2023.109733","article-title":"Exosome from adipose-derived mesenchymal stem cells attenuates scar formation through microRNA-181a\/SIRT1 axis","volume":"746","author":"Chen","year":"2023","journal-title":"Arch. Biochem. Biophys."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1242\/jcs.02932","article-title":"Mesenchymal stem cells reside in virtually all post-natal organs and tissues","volume":"119","author":"da Silva Meirelles","year":"2006","journal-title":"J. Cell Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"tkad036","DOI":"10.1093\/burnst\/tkad036","article-title":"Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids","volume":"12","author":"Dai","year":"2024","journal-title":"Burns Trauma"},{"key":"B12","doi-asserted-by":"publisher","first-page":"105564","DOI":"10.1016\/j.biocel.2019.105564","article-title":"Exosomes from adipose-derived mesenchymal stem cells ameliorate cardiac damage after myocardial infarction by activating S1P\/SK1\/S1PR1 signaling and promoting macrophage M2 polarization","volume":"114","author":"Deng","year":"2019","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1111\/ijd.15159","article-title":"Keloids: a review of therapeutic management","volume":"60","author":"Ekstein","year":"2021","journal-title":"Int. J. Dermatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.addr.2020.04.004","article-title":"Extracellular vesicles as drug delivery systems: why and how?","volume":"159","author":"Elsharkasy","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.2147\/ijn.S448905","article-title":"Plant-derived exosome-like nanoparticles: emerging nanosystems for enhanced tissue engineering","volume":"19","author":"Feng","year":"2024","journal-title":"Int. J. Nanomedicine"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2244","DOI":"10.1161\/strokeaha.108.541128","article-title":"Update of the stroke therapy academic industry roundtable preclinical recommendations","volume":"40","author":"Fisher","year":"2009","journal-title":"Stroke"},{"key":"B17","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s40257-022-00744-6","article-title":"Hypertrophic scars and keloids: advances in treatment and review of established therapies","volume":"24","author":"Frech","year":"2023","journal-title":"Am. J. Clin. Dermatol"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.1006\/jsre.1993.1132","article-title":"Regulation of collagen gene expression in keloids and hypertrophic scars","author":"Friedman","year":"1993"},{"key":"B19","doi-asserted-by":"publisher","first-page":"113","DOI":"10.2119\/molmed.2009.00153","article-title":"Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies","volume":"17","author":"Gauglitz","year":"2011","journal-title":"Mol. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1444964","DOI":"10.3389\/fimmu.2024.1444964","article-title":"Macrophage polarization and its impact on idiopathic pulmonary fibrosis","volume":"15","author":"Ge","year":"2024","journal-title":"Front. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1046\/j.1524-475x.2000.00083.x","article-title":"Models for use in wound healing research: a survey focusing on in vitro and in vivo adult soft tissue","volume":"8","author":"Gottrup","year":"2000","journal-title":"Wound Repair Regen."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.3390\/cells10081959","article-title":"Mesenchymal stem cell-derived exosomes: applications in regenerative medicine","volume":"10","author":"Hade","year":"2021","journal-title":"Cells"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1166\/jbn.2017.2474","article-title":"Microneedles-based transdermal drug delivery systems: a review","volume":"13","author":"Hao","year":"2017","journal-title":"J. Biomed. Nanotechnol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.retram.2016.09.003","article-title":"The role of myofibroblasts in wound healing","volume":"64","author":"Hinz","year":"2016","journal-title":"Curr. Res. Transl. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2730","DOI":"10.1091\/mbc.12.9.2730","article-title":"Alpha-smooth muscle actin expression upregulates fibroblast contractile activity","volume":"12","author":"Hinz","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.3390\/biomedicines11041056","article-title":"Human in vitro skin models for wound healing and wound healing disorders","volume":"11","author":"Hofmann","year":"2023","journal-title":"Biomedicines"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1285087","DOI":"10.1155\/2021\/1285087","article-title":"Stem cell-derived nanovesicles: a novel cell-free therapy for wound healing","volume":"2021","author":"Huang","year":"2021","journal-title":"Stem Cells Int."},{"key":"B29","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41419-020-2510-4","article-title":"Exosomes derived from hucMSC attenuate renal fibrosis through CK1\u03b4\/\u03b2-TRCP-mediated YAP degradation","volume":"11","author":"Ji","year":"2020","journal-title":"Cell Death Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.biochi.2020.08.003","article-title":"Exosomes derived from TSG-6 modified mesenchymal stromal cells attenuate scar formation during wound healing","volume":"177","author":"Jiang","year":"2020","journal-title":"Biochimie"},{"key":"B31","doi-asserted-by":"publisher","first-page":"a041222","DOI":"10.1101\/cshperspect.a041222","article-title":"Diversity of fibroblasts and their roles in wound healing","volume":"15","author":"Jiang","year":"2023","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"6742","DOI":"10.3390\/ijms23126742","article-title":"Extracellular vesicles in facial aesthetics: a review","volume":"23","author":"Kee","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"8776","DOI":"10.3390\/ijms25168776","article-title":"Comprehensive insights into keloid pathogenesis and advanced therapeutic strategies","volume":"25","author":"Kim","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1097\/PRS.0b013e3182a8070c","article-title":"Update on scar management: guidelines for treating Asian patients","volume":"132","author":"Kim","year":"2013","journal-title":"Plast. Reconstr. Surg."},{"key":"B35","doi-asserted-by":"crossref","DOI":"10.3390\/ijms252111579","article-title":"An update on molecular mechanisms of Scarring-A narrative review","author":"Kohlhauser","year":"2024"},{"key":"B36","doi-asserted-by":"publisher","first-page":"30087","DOI":"10.3402\/jev.v4.30087","article-title":"Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper","volume":"4","author":"Lener","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"B37","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1186\/s13287-021-02290-0","article-title":"Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p\/IL-17RA\/Smad axis","volume":"12","author":"Li","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"B38","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1002\/hcs2.70028","article-title":"Exploring regulatory frameworks for exosome therapy: insights and perspectives","volume":"4","author":"Li","year":"2025","journal-title":"Health Care Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1111\/wrr.12398","article-title":"Transforming growth factor beta (TGF-\u03b2) isoforms in wound healing and fibrosis","volume":"24","author":"Lichtman","year":"2016","journal-title":"Wound Repair Regen."},{"key":"B40","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1111\/bjd.18219","article-title":"Hypertrophic and keloid scars fail to progress from the CD34(-)\/\u03b1-smooth muscle actin (\u03b1-SMA)(+) immature scar phenotype and show gradient differences in \u03b1-SMA and p16 expression","volume":"182","author":"Limandjaja","year":"2020","journal-title":"Br. J. Dermatol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1111\/exd.14121","article-title":"Hypertrophic scars and keloids: overview of the evidence and practical guide for differentiating between these abnormal scars","volume":"30","author":"Limandjaja","year":"2021","journal-title":"Exp. Dermatol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.jconrel.2022.05.062","article-title":"Engineered extracellular vesicles and their mimetics for cancer immunotherapy","volume":"349","author":"Liu","year":"2022","journal-title":"J. Control Release"},{"key":"B43","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1186\/s13287-024-03928-5","article-title":"Adipose stem cell exosomes promote mitochondrial autophagy through the PI3K\/AKT\/mTOR pathway to alleviate keloids","volume":"15","author":"Liu","year":"2024","journal-title":"STEM CELL Res. & Ther."},{"key":"B44","doi-asserted-by":"publisher","first-page":"9565","DOI":"10.1039\/d2tb01987f","article-title":"Advances in microRNA from adipose-derived mesenchymal stem cell-derived exosome: focusing on wound healing","volume":"10","author":"Ma","year":"2022","journal-title":"J. Mater Chem. B"},{"key":"B45","doi-asserted-by":"publisher","first-page":"440","DOI":"10.3724\/abbs.2023274","article-title":"HSFAS mediates fibroblast proliferation, migration, trans-differentiation and apoptosis in hypertrophic scars via interacting with ADAMTS8","volume":"56","author":"Ma","year":"2024","journal-title":"Acta Biochim. Biophys. Sin. (Shanghai)"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e2305374","DOI":"10.1002\/smll.202305374","article-title":"MiR-141-3p-Functionalized exosomes loaded in dissolvable microneedle arrays for hypertrophic scar treatment","volume":"20","author":"Meng","year":"2024","journal-title":"Small"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.jconrel.2022.12.027","article-title":"Hybrid exosomes, exosome-like nanovesicles and engineered exosomes for therapeutic applications","volume":"353","author":"Mondal","year":"2023","journal-title":"J. Control Release"},{"key":"B48","doi-asserted-by":"publisher","first-page":"654210","DOI":"10.3389\/fcell.2021.654210","article-title":"Mesenchymal stromal cell-conditioned medium for skin diseases: a systematic review","volume":"9","author":"Montero-Vilchez","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"4674","DOI":"10.3390\/ijms25094674","article-title":"Pharmacotherapy for keloids and hypertrophic scars","volume":"25","author":"Murakami","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"10410","DOI":"10.3390\/ijms231810410","article-title":"Mast cells are activated in the giant earlobe keloids: a case series","volume":"23","author":"Nakajima","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B51","doi-asserted-by":"crossref","DOI":"10.3390\/ijms18030606","article-title":"Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis","author":"Ogawa","year":"2017"},{"key":"B52","doi-asserted-by":"publisher","first-page":"79e","DOI":"10.1097\/prs.0000000000008667","article-title":"The Most current algorithms for the treatment and prevention of hypertrophic scars and keloids: a 2020 update of the algorithms published 10 years ago","volume":"149","author":"Ogawa","year":"2022","journal-title":"Plast. Reconstr. Surg."},{"key":"B53","doi-asserted-by":"publisher","first-page":"3212643","DOI":"10.1155\/2018\/3212643","article-title":"Extracellular vesicles from amnion-derived mesenchymal stem cells ameliorate hepatic inflammation and fibrosis in rats","volume":"2018","author":"Ohara","year":"2018","journal-title":"Stem Cells Int."},{"key":"B54","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"Bmj"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e6021","DOI":"10.1097\/gox.0000000000006021","article-title":"Exosome-mediated advancements in plastic surgery: navigating therapeutic potential in skin rejuvenation and wound healing","volume":"12","author":"Park","year":"2024","journal-title":"Plast. Reconstr. Surg. Glob. Open"},{"key":"B56","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1186\/s13287-019-1484-6","article-title":"Functional proteins of mesenchymal stem cell-derived extracellular vesicles","volume":"10","author":"Qiu","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1326728","DOI":"10.3389\/fimmu.2024.1326728","article-title":"Development and validation of novel keloid-derived immortalized fibroblast cell lines","volume":"15","author":"Sadiq","year":"2024","journal-title":"Front. Immunol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1089\/wound.2021.0026","article-title":"Human wound and its burden: updated 2020 compendium of estimates","volume":"10","author":"Sen","year":"2021","journal-title":"Adv. Wound Care (New Rochelle)"},{"key":"B59","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1089\/wound.2023.0150","article-title":"Human wound and its burden: updated 2022 compendium of estimates","volume":"12","author":"Sen","year":"2023","journal-title":"Adv. Wound Care (New Rochelle)"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1089\/scd.2014.0316","article-title":"Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro","volume":"24","author":"Shabbir","year":"2015","journal-title":"Stem Cells Dev."},{"key":"B61","doi-asserted-by":"publisher","first-page":"6352","DOI":"10.1021\/acsnano.0c07714","article-title":"Sequential release of small extracellular vesicles from bilayered thiolated alginate\/polyethylene glycol diacrylate hydrogels for scarless wound healing","volume":"15","author":"Shen","year":"2021","journal-title":"ACS Nano"},{"key":"B62","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1186\/s13287-021-02296-8","article-title":"Extracellular vesicles derived from umbilical cord mesenchymal stromal cells alleviate pulmonary fibrosis by means of transforming growth factor-\u03b2 signaling inhibition","volume":"12","author":"Shi","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"B63","doi-asserted-by":"publisher","first-page":"924244","DOI":"10.3389\/fimmu.2022.924244","article-title":"Dynamically upregulated mast cell CPA3 patterns in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis","volume":"13","author":"Siddhuraj","year":"2022","journal-title":"Front. Immunol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"2787","DOI":"10.1083\/jcb.103.6.2787","article-title":"A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation","volume":"103","author":"Skalli","year":"1986","journal-title":"J. Cell Biol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1046\/j.1524-475x.2001.00066.x","article-title":"The pig as a model for human wound healing","volume":"9","author":"Sullivan","year":"2001","journal-title":"Wound Repair Regen."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/j.stemcr.2015.05.004","article-title":"Expression of \u03b1-Smooth muscle actin determines the fate of mesenchymal stromal cells","volume":"4","author":"Talele","year":"2015","journal-title":"Stem Cell Rep."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.3389\/fimmu.2019.01810","article-title":"Understanding keloid pathobiology from a quasi-neoplastic perspective: less of a scar and more of a chronic inflammatory disease with cancer-like tendencies","volume":"10","author":"Tan","year":"2019","journal-title":"Front. Immunol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"3493","DOI":"10.1113\/jp274492","article-title":"Transforming growth factor-\u03b2 signalling in renal fibrosis: from smads to non-coding RNAs","volume":"596","author":"Tang","year":"2018","journal-title":"J. Physiol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/nri855","article-title":"Exosomes: composition, biogenesis and function","volume":"2","author":"Th\u00e9ry","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1186\/s12967-015-0642-6","article-title":"LPS-Preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b","volume":"13","author":"Ti","year":"2015","journal-title":"J. Transl. Med."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1431846","DOI":"10.3389\/fphar.2024.1431846","article-title":"Human adipose mesenchymal stem cell-derived exosomes alleviate fibrosis by restraining ferroptosis in keloids","volume":"15","author":"Tian","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s41702-020-00063-8","article-title":"Hypertrophic scars and keloids: a review and current treatment modalities","volume":"4","author":"Tripathi","year":"2020","journal-title":"Biomed. Dermatol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.2147\/ccid.S520913","article-title":"Exosome-loaded GelMA hydrogel as a cell-free therapeutic strategy for hypertrophic scar inhibition","volume":"18","author":"Wang","year":"2025","journal-title":"Clin. Cosmet. Investig. Dermatol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"tkad064","DOI":"10.1093\/burnst\/tkad064","article-title":"miR-125b-5p delivered by adipose-derived stem cell exosomes alleviates hypertrophic scarring by suppressing Smad2","volume":"12","author":"Xu","year":"2024","journal-title":"Burns Trauma"},{"key":"B75","doi-asserted-by":"publisher","first-page":"216","DOI":"10.3892\/mmr.2024.13340","article-title":"Exosomal miR-194 from adipose-derived stem cells impedes hypertrophic scar formation through targeting TGF-\u03b21","volume":"30","author":"Xu","year":"2024","journal-title":"Mol. Med. Rep."},{"key":"B76","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1007\/s11033-025-10794-8","article-title":"Personalized human umbilical cord mesenchymal stem cell-derived exosome pre-treatment based on the simulation of scar microenvironment characteristics: a promising approach for early scar treatment","volume":"52","author":"Ye","year":"2025","journal-title":"Mol. Biol. Rep."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1339336","DOI":"10.3389\/fimmu.2024.1339336","article-title":"Revisiting roles of mast cells and neural cells in keloid: exploring their connection to disease activity","volume":"15","author":"Yeo","year":"2024","journal-title":"Front. Immunol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40364-019-0159-x","article-title":"Exosomes from mesenchymal stem\/stromal cells: a new therapeutic paradigm","volume":"7","author":"Yin","year":"2019","journal-title":"Biomark. Res."},{"key":"B79","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/s41580-024-00716-0","article-title":"Fibroblast and myofibroblast activation in normal tissue repair and fibrosis","volume":"25","author":"Younesi","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"758","DOI":"10.3892\/mmr.2021.12398","article-title":"Exosomes from miR-29a-modified adipose-derived mesenchymal stem cells reduce excessive scar formation by inhibiting TGF-\u03b22\/Smad3 signaling","volume":"24","author":"Yuan","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"B81","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1089\/wound.2020.1348","article-title":"Vascular and collagen target: a rational approach to hypertrophic scar management","volume":"12","author":"Yuan","year":"2023","journal-title":"Adv. Wound Care (New Rochelle)"},{"key":"B82","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1111\/iwj.14081","article-title":"Exosome derived from human adipose-derived stem cell improve wound healing quality: a systematic review and meta-analysis of preclinical animal studies","volume":"20","author":"Yuan","year":"2023","journal-title":"Int. Wound J."},{"key":"B83","doi-asserted-by":"publisher","first-page":"110287","DOI":"10.1016\/j.biopha.2020.110287","article-title":"Current potential therapeutic strategies targeting the TGF-\u03b2\/Smad signaling pathway to attenuate keloid and hypertrophic scar formation","volume":"129","author":"Zhang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"B84","doi-asserted-by":"publisher","first-page":"720","DOI":"10.3390\/ijms22020720","article-title":"Topical application of mesenchymal stem cell exosomes alleviates the imiquimod induced psoriasis-like inflammation","volume":"22","author":"Zhang","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B85","doi-asserted-by":"publisher","first-page":"tkae062","DOI":"10.1093\/burnst\/tkae062","article-title":"Engineered extracellular vesicles for tissue repair and regeneration","volume":"12","author":"Zhang","year":"2024","journal-title":"Burns Trauma"},{"key":"B86","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s12951-025-03157-9","article-title":"Epidermal stem cell derived exosomes-induced dedifferentiation of myofibroblasts inhibits scarring via the miR-203a-3p\/PIK3CA axis","volume":"23","author":"Zhao","year":"2025","journal-title":"J. Nanobiotechnology"},{"key":"B87","doi-asserted-by":"publisher","first-page":"e70160","DOI":"10.1002\/jev2.70160","article-title":"Epidermal stem cell-derived extracellular vesicles induce fibroblasts mesenchymal-epidermal transition to alleviate hypertrophic scar formation via miR-200s inhibition of ZEB1 and 2","volume":"14","author":"Zhen","year":"2025","journal-title":"J. Extracell. Vesicles"},{"key":"B88","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/s13287-023-03345-0","article-title":"Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing","volume":"14","author":"Zhou","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"B89","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1097\/sap.0000000000002357","article-title":"Extracellular vesicles derived from human adipose-derived stem cell prevent the formation of hypertrophic scar in a rabbit model","volume":"84","author":"Zhu","year":"2020","journal-title":"Ann. Plast. Surg."},{"key":"B90","doi-asserted-by":"publisher","first-page":"e3688","DOI":"10.1002\/jgm.3688","article-title":"MEG3 shuttled by exosomes released from human bone marrow mesenchymal stem cells promotes TP53 stability to regulate MCM5 transcription in keloid fibroblasts","volume":"26","author":"Zhu","year":"2024","journal-title":"J. Gene Med."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1739106\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:14:04Z","timestamp":1771924444000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1739106\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":90,"alternative-id":["10.3389\/fcell.2026.1739106"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1739106","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]},"article-number":"1739106"}}