Platelet-Derived Microparticles Mediate the Intra-Articular Homing of Mesenchymal Stem Cells in Early-Stage Cartilage Lesions

Abstract

After intra-articular injection, synovium-derived mesenchymal stem cells (SMSCs) can adhere to damaged cartilage (a process called homing) and then repair the cartilage defect. Nonetheless, the main obstacle of the current method is the insufficient homing ratio of SMSCs, which fails to meet the requirements for cartilage repair and thereby greatly limits the therapeutic effect. In this study, the optimal homing time of SMSCs was determined by evaluating the SMSC homing efficiency at 1, 3, 7, 14, and 28 days after injury using a rat cartilage defect model. The ability of platelet-derived microparticles (PMPs) to promote SMSC homing was evaluated by cartilage/subchondral bone cell adhesion, transmembrane migration, and intra-articular cell distribution assays. SMSCs had an optimal homing efficiency in the very early stage (1 day) after cartilage injury. We found that PMPs, which were abundant in the synovial fluid at this early stage, were responsible for this augmented SMSC homing. An ex vivo cell adhesion assay revealed that the coincubation of SMSCs with PMPs at a 1:50 ratio markedly enhanced cell adhesion to cartilage and the subchondral bone surface. The transmembrane cell migration assay yielded similar results. Further in vivo homing assays revealed that PMPs possess excellent homing capacity, which they transferred, to some extent, to SMSCs by coating the cell surface. We measured the expression of homing-related genes in SMSCs exposed to PMPs and identified several upregulated genes. Moreover, platelet-specific adhesion molecules, particularly GPIIb/IIIa, CXCR4, ITGβ1, and ITGα2, were determined to play a critical role in the homing of SMSC/PMP complexes. This improvement in SMSC homing increased the volume of regenerated tissue in the cartilage defect. In conclusion, PMPs significantly promoted the homing of SMSCs to cartilage, which facilitated cartilage regeneration. These data suggest a safe and promising strategy for improving the outcome of stem cell therapy.