Keng Lin Wong1, Shipin Zhang2, Ming Wang3, Xiafei Ren3, Hassan Afizah3, Ruenn Chai Lai4, Sai Kiang Lim5, Eng Hin Lee6, James Hoi Po Hui6, Wei Seong Toh7. 1. Department of Orthopaedic Surgery, Sengkang General Hospital, Singhealth; Departments of Orthopaedic Surgery, Singapore. 2. Departments of Orthopaedic Surgery, Singapore; Faculty of Dentistry, Singapore. 3. Departments of Orthopaedic Surgery, Singapore. 4. National University of Singapore; and Institute of Medical Biology, Agency for Science, Technology and Research, Singapore. 5. Surgery, Yong Loo Lin School of Medicine, Singapore; National University of Singapore; and Institute of Medical Biology, Agency for Science, Technology and Research, Singapore. 6. Departments of Orthopaedic Surgery, Singapore; Tissue Engineering Program, Life Sciences Institute, Singapore. 7. Faculty of Dentistry, Singapore; Tissue Engineering Program, Life Sciences Institute, Singapore; Graduate School for Integrative Sciences & Engineering, Singapore. Electronic address: dentohws@nus.edu.sg.
Abstract
PURPOSE: To compare the efficacy of mesenchymal stem cell (MSC) exosomes with hyaluronic acid (HA) against HA alone for functional cartilage regeneration in a rabbit osteochondral defect model. METHODS: Critical-size osteochondral defects (4.5-mm diameter and 1.5-mm depth) were created on the trochlear grooves in the knees of 18 rabbits and were randomly allocated to 2 treatment groups: (1) exosomes and HA combination and (2) HA alone. Three 1-mL injections of either exosomes and HA or HA alone were administered intra-articularly immediately after surgery and thereafter at 7 and 14 days after surgery. At 6 and 12 weeks, gross evaluation, histologic and immunohistochemical analysis, and scoring were performed. The functional biomechanical competence of the repaired cartilage also was evaluated. RESULTS: Compared with defects treated with HA, defects treated with exosomes and HA showed significant improvements in macroscopic scores (P = .032; P = .001) and histologic scores (P = .005; P < .001) at 6 and 12 weeks, respectively. Defects treated with exosomes and HA also demonstrated improvements in mechanical properties compared with HA-treated defects, with significantly greater Young's moduli (P < .05) and stiffness (P < .05) at 6 and 12 weeks. By 12 weeks, the newly-repaired tissues in defects treated with exosomes and HA composed mainly of hyaline cartilage that are mechanically and structurally superior to that of HA-treated defects and demonstrated mechanical properties that approximated that of adjacent native cartilage (P > .05). In contrast, HA-treated defects showed some repair at 6 weeks, but this was not sustained, as evidenced by significant deterioration of histologic scores (P = .002) and a plateau in mechanical properties from 6 to 12 weeks. CONCLUSIONS: This study shows that the combination of MSC exosomes and HA administered at a clinically acceptable frequency of 3 intra-articular injections can promote sustained and functional cartilage repair in a rabbit post-traumatic cartilage defect model, when compared with HA alone. CLINICAL RELEVANCE: Human MSC exosomes and HA administered in combination promote functional cartilage repair and may represent a promising cell-free therapy for cartilage repair in patients.
PURPOSE: To compare the efficacy of mesenchymal stem cell (MSC) exosomes with hyaluronic acid (HA) against HA alone for functional cartilage regeneration in a rabbit osteochondral defect model. METHODS: Critical-size osteochondral defects (4.5-mm diameter and 1.5-mm depth) were created on the trochlear grooves in the knees of 18 rabbits and were randomly allocated to 2 treatment groups: (1) exosomes and HA combination and (2) HA alone. Three 1-mL injections of either exosomes and HA or HA alone were administered intra-articularly immediately after surgery and thereafter at 7 and 14 days after surgery. At 6 and 12 weeks, gross evaluation, histologic and immunohistochemical analysis, and scoring were performed. The functional biomechanical competence of the repaired cartilage also was evaluated. RESULTS: Compared with defects treated with HA, defects treated with exosomes and HA showed significant improvements in macroscopic scores (P = .032; P = .001) and histologic scores (P = .005; P < .001) at 6 and 12 weeks, respectively. Defects treated with exosomes and HA also demonstrated improvements in mechanical properties compared with HA-treated defects, with significantly greater Young's moduli (P < .05) and stiffness (P < .05) at 6 and 12 weeks. By 12 weeks, the newly-repaired tissues in defects treated with exosomes and HA composed mainly of hyaline cartilage that are mechanically and structurally superior to that of HA-treated defects and demonstrated mechanical properties that approximated that of adjacent native cartilage (P > .05). In contrast, HA-treated defects showed some repair at 6 weeks, but this was not sustained, as evidenced by significant deterioration of histologic scores (P = .002) and a plateau in mechanical properties from 6 to 12 weeks. CONCLUSIONS: This study shows that the combination of MSC exosomes and HA administered at a clinically acceptable frequency of 3 intra-articular injections can promote sustained and functional cartilage repair in a rabbit post-traumatic cartilage defect model, when compared with HA alone. CLINICAL RELEVANCE: Human MSC exosomes and HA administered in combination promote functional cartilage repair and may represent a promising cell-free therapy for cartilage repair in patients.
Authors: Jolene Phelps; Catherine Leonard; Sophia Shah; Roman Krawetz; David A Hart; Neil A Duncan; Arindom Sen Journal: Stem Cells Transl Med Date: 2022-03-03 Impact factor: 7.655
Authors: Marietta Herrmann; Solvig Diederichs; Svitlana Melnik; Jana Riegger; Drenka Trivanović; Shushan Li; Zsuzsa Jenei-Lanzl; Rolf E Brenner; Markus Huber-Lang; Frank Zaucke; Frank A Schildberg; Susanne Grässel Journal: Front Bioeng Biotechnol Date: 2021-01-20
Authors: Kris T C Hede; Bjørn B Christensen; Morten L Olesen; Jesper Skovhus Thomsen; Casper B Foldager; Wei Seong Toh; Sai Kiang Lim; Martin C Lind Journal: Cartilage Date: 2021-07-26 Impact factor: 3.117