CHONDROCYTIC POTENTIAL OF ALLOGENIC MESENCHYMAL STEM CELLS TRANSPLANTED WITHOUT IMMUNOSUPPRESSION TO REGENERATE PHYSEAL DEFECT IN RABBITS

Abstract

Mesenchymal stem cells (MSCs) from bone marrow are multipotent cells capable of forming cartilage, bone, and other connective tissues. The objective of this study was to determine whether the use of allogenic mesenchymal stem cells could functionally heal defect in the distal femoral physis in rabbits without the use of immunosuppressive therapy. An iatrogenic defect was created in the lateral femoral condyle of thirty-two New Zealand white rabbits, 7 weeks old, that weighed 2.25 ? 0.24 kg. Each defect, 3.5 mm in width and 12 mm in length, in the right distal femoral physis was treated with allogenic mesenchymal stem cells in new composite hyaluronate/ collagen type I/fibrin scaffold. The healing response was evaluated radiographically, by MRI (at three weeks and four months after implantation), and also histologically, by Pearls’ reaction and with immunofluorescency (at four months after implantation). The results were compared with the data for the control defects (without stem cell implantation) in left distal femoral physes. In average, right femurs with damaged distal physis and transplanted MSCs grew more in length (0.55? 0.21 cm) as compared with left femurs with physeal defect without stem cell transplantation (0.46? 0.23 cm). Valgus deformity of right femurs with physeal defect and transplanted MSCs was mild (0.2? 0.1°). On the contrary, left femurs with physeal defect without transplantated MSCs showed significant valgus deformity (2.7? 1.6°). For defects treated with allogenic mesenchymal stem cell implants, no adverse immune response and implant rejection were detected in this model. Histologically, no lymphocytic infiltration occurred. At four months after transplantation, hyalinne cartilage had formed throughout the defects treated with allogenic MSCs. Labeled mesenchymal stem cells/diferentiated chondrocytes were detected in the physeal defects based on magnetic resonance imaging and immunofluorescency. The results of this study demonstrated that allogenic mesenchymal stem cells in a new composite hyaluronate/collagen type I/fibrin scaffold repaired iatrogenic defects in the distal femoral physes in rabbits without the use of immunosuppressive therapy. The use of allogenic mesenchymal stem cells for the repair of physeal defects may be an alternative to autologous MSCs transplantation. An allogenic approach would enable mesenchymal stem cells to be isolated from any donor, providing a readily available source of cells for cartilage tissue repair.