{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:47:27Z","timestamp":1787755647795,"version":"build-2784847793"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,6,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The objective of this study was to examine the therapeutic effects of human mesenchymal stromal\/stem cell (MSC) exosomes in a rat model of growth plate injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A growth plate defect was surgically created on the distal part of the right femur of 40 female Sprague-Dawley rats. A single intra-articular injection of 100 \u00b5g of MSC exosomes in 100 \u00b5L of phosphate-buffered saline solution (PBS), or an equivalent volume of PBS alone, was administered to the right knee immediately after surgery. At 4 and 8 weeks post-treatment, limb length was measured with micro-CT, and tissue repair was assessed with histological, immunohistochemical, and histomorphometric analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>A single injection of MSC exosomes significantly increased limb length from 3.29 \u00b1 0.07 cm at 4 weeks to 3.37 \u00b1 0.11 cm at 8 weeks (p = 0.047). However, no improvement in limb length was observed in the PBS control group. The limb-length discrepancy between the involved limb and the contralateral limb in the exosome-treated group was significantly less than the discrepancy in the PBS-treated group at both 4 weeks (2.52% \u00b1 1.30% versus 4.11% \u00b1 0.93%; p = 0.006) and 8 weeks (5.27% \u00b1 2.11% versus 8.06% \u00b1 2.56%; p = 0.016). Consistent with the reduced limb-length discrepancy, the exosome-treated defects displayed significantly more chondrocytes (p &lt; 0.05) and a higher area percentage with deposition of sulphated glycosaminoglycan (p &lt; 0.05) and collagen II (p &lt; 0.05) than PBS-treated defects at 8 weeks. However, bone bridge formation was not inhibited in either group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>A single intra-articular injection of MSC exosomes significantly enhanced physeal repair and reduced limb-length discrepancy but did not inhibit bone-bridge formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>This proof-of-concept study demonstrates for the first time the potential use of MSC exosomes as a minimally invasive cell-free therapeutic to promote physeal repair and reduce limb-length discrepancy following growth plate injuries.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2106\/jbjs.21.00789","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T15:17:52Z","timestamp":1645111072000},"page":"1098-1106","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Mesenchymal Stem Cell Exosomes Promote Growth Plate Repair and Reduce Limb-Length Discrepancy in Young Rats"],"prefix":"10.2106","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2100-8269","authenticated-orcid":false,"given":"Keng Lin","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Department of Orthopaedic Surgery, Sengkang General Hospital, Singhealth, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8421-7108","authenticated-orcid":false,"given":"Shipin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Faculty of Dentistry, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0075-7890","authenticated-orcid":false,"given":"Sharon Si Heng","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-5104","authenticated-orcid":false,"given":"Yi Ann","family":"Cheow","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4636-8535","authenticated-orcid":false,"given":"Ruenn Chai","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5752-3297","authenticated-orcid":false,"given":"Sai Kiang","family":"Lim","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore"},{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1130-4558","authenticated-orcid":false,"given":"James Hoi Po","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Tissue Engineering Program, Life Sciences Institute, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9147-6423","authenticated-orcid":false,"given":"Wei Seong","family":"Toh","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Faculty of Dentistry, National University of Singapore, Singapore"},{"name":"Tissue Engineering Program, Life Sciences Institute, National University of Singapore, Singapore"},{"name":"Integrative Sciences and Engineering Program, NUS Graduate School, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"issue":"11","key":"bib1-20250430","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1007\/s11999-016-4891-3","article-title":"Classifications In Brief: Salter-Harris Classification of Pediatric Physeal Fractures","volume":"474","author":"Cepela","year":"2016","journal-title":"Clin Orthop Relat Res."},{"issue":"1","key":"bib2-20250430","doi-asserted-by":"crossref","first-page":"T45","DOI":"10.1530\/JME-14-0062","article-title":"Recent research on the growth plate: Mechanisms for growth plate injury repair and potential cell-based therapies for regeneration","volume":"53","author":"Chung","year":"2014","journal-title":"J Mol Endocrinol."},{"issue":"9","key":"bib3-20250430","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1097\/BOT.0b013e3181a4f25b","article-title":"Growth disturbance after distal femoral growth plate fractures in children: a meta-analysis","volume":"23","author":"Basener","year":"2009","journal-title":"J Orthop Trauma."},{"key":"bib4-20250430","doi-asserted-by":"crossref","first-page":"53","DOI":"10.22203\/eCM.v015a05","article-title":"Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts","volume":"15","author":"Shapiro","year":"2008","journal-title":"Eur Cell Mater."},{"issue":"2","key":"bib5-20250430","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.orthres.2003.08.003","article-title":"Intramembranous ossification mechanism for bone bridge formation at the growth plate cartilage injury site","volume":"22","author":"Xian","year":"2004","journal-title":"J Orthop Res."},{"issue":"2","key":"bib6-20250430","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/01241398-200403000-00014","article-title":"Chitin as a scaffold for mesenchymal stem cells transfers in the treatment of partial growth arrest","volume":"24","author":"Li","year":"2004","journal-title":"J Pediatr Orthop."},{"issue":"4","key":"bib7-20250430","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/01241398-200307000-00002","article-title":"Cultured mesenchymal stem cell transfers in the treatment of partial growth arrest","volume":"23","author":"Chen","year":"2003","journal-title":"J Pediatr Orthop."},{"key":"bib8-20250430","doi-asserted-by":"crossref","first-page":"204","DOI":"10.2174\/1874325001004010204","article-title":"Application of autologous bone marrow derived mesenchymal stem cells to an ovine model of growth plate cartilage injury","volume":"4","author":"McCarty","year":"2010","journal-title":"Open Orthop J."},{"issue":"3","key":"bib9-20250430","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.scr.2009.12.003","article-title":"Exosome secreted by MSC reduces myocardial ischemia\/reperfusion injury","volume":"4","author":"Lai","year":"2010","journal-title":"Stem Cell Res."},{"issue":"1","key":"bib10-20250430","doi-asserted-by":"crossref","first-page":"1609206","DOI":"10.1080\/20013078.2019.1609206","article-title":"Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications","volume":"8","author":"Witwer","year":"2019","journal-title":"J Extracell Vesicles."},{"issue":"12","key":"bib11-20250430","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1016\/j.joca.2016.06.022","article-title":"Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration","volume":"24","author":"Zhang","year":"2016","journal-title":"Osteoarthritis Cartilage."},{"key":"bib12-20250430","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.biomaterials.2017.11.028","article-title":"MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity","volume":"156","author":"Zhang","year":"2018","journal-title":"Biomaterials."},{"key":"bib13-20250430","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.biomaterials.2019.02.006","article-title":"MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis","volume":"200","author":"Zhang","year":"2019","journal-title":"Biomaterials."},{"issue":"8","key":"bib14-20250430","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1016\/j.arthro.2020.03.031","article-title":"Intra-Articular Injections of Mesenchymal Stem Cell Exosomes and Hyaluronic Acid Improve Structural and Mechanical Properties of Repaired Cartilage in a Rabbit Model","volume":"36","author":"Wong","year":"2020","journal-title":"Arthroscopy."},{"issue":"1","key":"bib15-20250430","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13287-016-0391-3","article-title":"Exosomes\/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K\/Akt signaling pathway","volume":"7","author":"Zhang","year":"2016","journal-title":"Stem Cell Res Ther."},{"issue":"6","key":"bib16-20250430","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1016\/j.bone.2010.02.017","article-title":"Characterization of a small animal growth plate injury model using microcomputed tomography","volume":"46","author":"Coleman","year":"2010","journal-title":"Bone."},{"issue":"1","key":"bib17-20250430","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1479-5876-9-47","article-title":"Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs","volume":"9","author":"Chen","year":"2011","journal-title":"J Transl Med."},{"issue":"10","key":"bib18-20250430","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1074\/mcp.M600393-MCP200","article-title":"Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells","volume":"6","author":"Sze","year":"2007","journal-title":"Mol Cell Proteomics."},{"issue":"1","key":"bib19-20250430","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Th\u00e9ry","year":"2018","journal-title":"J Extracell Vesicles."},{"issue":"5","key":"bib20-20250430","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.jcyt.2021.01.001","article-title":"Critical considerations for the development of potency tests for therapeutic applications of mesenchymal stromal cell-derived small extracellular vesicles","volume":"23","author":"Gimona","year":"2021","journal-title":"Cytotherapy."},{"issue":"7","key":"bib21-20250430","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1002\/jor.22330","article-title":"Basement membrane molecule expression attendant to chondrogenesis by nucleus pulposus cells and mesenchymal stem cells","volume":"31","author":"Toh","year":"2013","journal-title":"J Orthop Res."},{"key":"bib22-20250430","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.actbio.2019.03.021","article-title":"Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration","volume":"89","author":"Chew","year":"2019","journal-title":"Acta Biomater."},{"issue":"258","key":"bib23-20250430","doi-asserted-by":"crossref","first-page":"601990","DOI":"10.3389\/fcvm.2020.601990","article-title":"Systemic Mesenchymal Stem Cell-Derived Exosomes Reduce Myocardial Infarct Size: Characterization With MRI in a Porcine Model","volume":"7","author":"Charles","year":"2020","journal-title":"Front Cardiovasc Med."},{"issue":"4","key":"bib24-20250430","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.bone.2011.07.024","article-title":"Structural and molecular analyses of bone bridge formation within the growth plate injury site and cartilage degeneration at the adjacent uninjured area","volume":"49","author":"Macsai","year":"2011","journal-title":"Bone."},{"key":"bib25-20250430","doi-asserted-by":"crossref","first-page":"971907","DOI":"10.1155\/2012\/971907","article-title":"Proteolytic Potential of the MSC Exosome Proteome: Implications for an Exosome-Mediated Delivery of Therapeutic Proteasome","volume":"2012","author":"Lai","year":"2012","journal-title":"Int J Proteomics."},{"issue":"1","key":"bib26-20250430","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/nar\/gkp857","article-title":"Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs","volume":"38","author":"Chen","year":"2010","journal-title":"Nucleic Acids Res."}],"container-title":["Journal of Bone and Joint Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.2106\/JBJS.21.00789","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:45:59Z","timestamp":1787751959000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.2106\/JBJS.21.00789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,17]]},"references-count":26,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.2106\/jbjs.21.00789","relation":{},"ISSN":["0021-9355","1535-1386"],"issn-type":[{"value":"0021-9355","type":"print"},{"value":"1535-1386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,17]]}}}