2021 ISAKOS Biennial Congress Paper
Intra-Articular Mesenchymal Stem Cell Exosomes And Hyaluronic Acid Combination Therapy Promotes Safe And Functional Osteochondral Repair In A Porcine Model
Keng Lin Francis Wong, MMed(Orth), MCI (NUS), FRCSEd (Orth), FAMS, PhD, Singapore SINGAPORE
Shipin Zhang, PhD, Singapore, Singapore SINGAPORE
Xiafei Ren, PhD, Singapore, Singapore SINGAPORE
Ruenn Chai Lai, PhD, Singapore SINGAPORE
Sai Kiang Lim, PhD, Singapore SINGAPORE
James Hui, MBBS, FRCS, FAMS, M.D. (Orthopaedic Surgery), Singapore SINGAPORE
Wei Seong Toh, PhD, Singapore SINGAPORE
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, Singapore, SINGAPORE
FDA Status Not Applicable
Summary
Mesenchymal stem cell exosomes and hyaluronic acid combination administered at a clinically acceptable frequency of three intra-articular injections promote osteochondral repair with significantly improved morphological, histological, and biomechanical outcomes in a clinically relevant porcine model.
Abstract
Purpose
We had previously reported the efficacy of human mesenchymal stem cell (MSC) exosomes in repair of critical-size osteochondral defects in rats and rabbits. To enable clinical translation of MSC exosomes, we proposed a validation of the efficacy of MSC exosomes in a large animal model.
Materials & Methods: Bilateral osteochondral defects (6mm diameter and 1mm depth) were surgically created on the medial femoral condyles of 24 knees in 12 micropigs. Immediately after surgery and at days 8 and 15 post-surgery, 6 micropigs in exosome/HA group received sequential administration of 1mg exosomes in 1ml phosphate-buffered saline (PBS) followed by 1ml hyaluronic acid (HA; Synvisc®) in both knees, whereas the other 6 micropigs in the HA group received 1ml of PBS followed by 1ml HA in both knees. Except for MRI performed on day 15, 2 and 4 months, macroscopic, histological, biomechanical, and micro-CT assessments were performed at 4 months.
Results
At 4 months, exosome/HA-treated defects had significantly higher MRI scores than that for HA-treated defects at day 15 (4.46 vs 3.63; P=0.017), 2 months (7.83 vs 5.79; P=0.023) and 4 months (9.25 vs 6.71; P=0.024). Exosome/HA-treated defects also had significantly better ICRS macroscopic score (9.22 vs 7.25; P=0.008) and ICRS II histological score (79.71 vs 65.10; P=0.032) than HA-treated defects. The mean Young’s moduli of exosome/HA-treated defects were higher than that of HA-treated defects in the defect periphery (19.92 vs 5.50MPa; P=0.003) but modestly in the defect centre (15.17 vs 3.53MPa; P=0.119). Micro-CT analysis revealed structural improvements in the subchondral bone with significantly higher BV/TV and Tb.Th in exosome/HA-treated defects than in HA-treated defects. Importantly, no adverse responses or systemic alterations were observed.
Conclusion
MSC exosomes and HA combination administered at a clinically acceptable frequency of three intra-articular injections promote osteochondral repair with significantly improved morphological, histological, and biomechanical outcomes in a clinically relevant porcine model.