Platelet-rich plasma enhances local homing of umbilical cord-derived mesenchymal stem cells to articular cartilage by increasing the quantity and activation of integrin ꞵ1.

BACKGROUND: Enhancing mesenchymal stem cells (MSCs) engraftment at the degenerative cartilage is important to increase the therapeutic effect of cartilage regeneration. Platelet-rich plasma (PRP) is known to have anti-inflammatory and anabolic effects for the treatment of osteoarthritis and has been reported to be commonly used with MSCs. However, little is known about the effects of PRP on MSCs adhesion to cartilage extracellular matrix (ECM). The purpose of this study was to investigate how PRP pre-conditioning enhances MSC adhesion to cartilage ECM and improves the efficacy of MSCs in promoting cartilage regeneration in a rat osteochondral defect model. METHOD: In vitro adhesion of umbilical cord-derived MSCs (UC MSCs) to collagens, fibronectin, and hyaluronic acid and to osteochondral explants was measured with or without PRP pre-conditioning using a cell viability assay. The mRNA expression of integrin subunits and the activity level of integrin ꞵ1 (ITGB1) were evaluated using RT-PCR and western blot, respectively. After establishing an osteochondral defect in the femoral trochlea in Sprague-Dawley rats (n = 26), UC MSCs with PRP were locally injected into the defect. After 4 weeks, macroscopic and histological evaluations were performed using ICRS and O'Driscoll scoring systems. RESULTS: PRP significantly increased the adhesion of MSCs to collagens, fibronectin, and degenerative osteochondral explants, and this effect was inhibited primarily by ITGB1. Pre-conditioning of MSCs with PRP altered ITGB1 into an active form without cell-to-ECM interaction. Pre-conditioning UC MSCs and type II collagen with PRP prior to adhesion significantly enhanced their adhesion by 4.1-fold compared to the control. In histological evaluation, the O'Driscoll scores of UC MSCs (11.56 ± 0.53, p < .001) and UC MSCs + PRP group (14.13 ± 0.53, p < .001) were significantly higher than the control group (4.40 ± 0.82). PRP as a vehicle of MSCs showed a higher O'Driscoll score than MSCs with saline by 1.2-fold (p = .035). CONCLUSION: This suggests that pre-conditioning MSCs and cartilage ECM with PRP synergistically enhanced MSC adhesion to the cartilage ECM by increasing both the quantity and activation of ITGB1 in MSCs, thereby enhancing the therapeutic effects of MSCs on articular cartilage regeneration in a rat osteochondral defect model.