Synovial mesenchymal stem cells promote healing after meniscal repair in microminipigs

Abstract

The induction of synovial tissue to the meniscal lesion is crucial for meniscal healing. Synovial Mesenchymal stem cells (MSCs) are an attractive cell source because of their high proliferative and chondrogenic potentials. We examined whether transplantation of synovial MSCs promoted healing after meniscal repair of extended longitudinal tear of avascular area in a microminipig model. Longitudinal tear lesion was made in medial menisci and sutured in both knees, and then a synovial MSC suspension was administered for 10 min only in unilateral knee. The sutured meniscus was evaluated morphologically and biomechanically at 2, 4, and 12 weeks. The behavior of transplanted MSCs was also examined. The meniscal healing at 12 weeks was significantly better in the MSC group than in the control group; macroscopically, histologically and by T1rho mapping analysis. Transmission electron microscopic analysis demonstrated that the meniscus lesion was occupied by dense collagen fibrils only in the MSC group. Biomechanical analysis revealed that the tensile strength to failure of the meniscus higher in the MSC group than in the control group in each microminipig. Synovial tissue covered better along the superficial layer from the outer zone into the lesion of the meniscus in the MSC group at 2 and 4 weeks in each microminipig. Synovial MSCs labeled with ferucarbotran were detected in the meniscus lesion and adjacent synovium by MRI at 2 weeks. Transplantation of synovial MSCs promoted healing after meniscal repair with induction of synovium into the longitudinal tear in the avascular zone of meniscus in pigs.