Mesenchymal Stem Cell Exosomes Promote Growth Plate Repair and Reduce Limb-Length Discrepancy in Young Rats.

Autor:	Wong KL; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Department of Orthopaedic Surgery, Sengkang General Hospital, Singhealth, Singapore., Zhang S; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Faculty of Dentistry, National University of Singapore, Singapore., Tan SSH; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Cheow YA; Faculty of Dentistry, National University of Singapore, Singapore., Lai RC; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore., Lim SK; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore.; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Hui JHP; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Tissue Engineering Program, Life Sciences Institute, National University of Singapore, Singapore., Toh WS; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Faculty of Dentistry, National University of Singapore, Singapore.; Tissue Engineering Program, Life Sciences Institute, National University of Singapore, Singapore.; Integrative Sciences and Engineering Program, NUS Graduate School, National University of Singapore, Singapore.
Jazyk:	angličtina
Zdroj:	The Journal of bone and joint surgery. American volume [J Bone Joint Surg Am] 2022 Jun 15; Vol. 104 (12), pp. 1098-1106. Date of Electronic Publication: 2022 Feb 17.
DOI:	10.2106/JBJS.21.00789
Abstrakt:	Background: 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. Methods: 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 µg of MSC exosomes in 100 µL 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. Results: A single injection of MSC exosomes significantly increased limb length from 3.29 ± 0.07 cm at 4 weeks to 3.37 ± 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% ± 1.30% versus 4.11% ± 0.93%; p = 0.006) and 8 weeks (5.27% ± 2.11% versus 8.06% ± 2.56%; p = 0.016). Consistent with the reduced limb-length discrepancy, the exosome-treated defects displayed significantly more chondrocytes (p < 0.05) and a higher area percentage with deposition of sulphated glycosaminoglycan (p < 0.05) and collagen II (p < 0.05) than PBS-treated defects at 8 weeks. However, bone bridge formation was not inhibited in either group. Conclusions: A single intra-articular injection of MSC exosomes significantly enhanced physeal repair and reduced limb-length discrepancy but did not inhibit bone-bridge formation. Clinical Relevance: 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. Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G937). (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)
Databáze:	MEDLINE
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