Prevention of Bone Bridge Formation Using Transplantation of the Autogenous Mesenchymal Stem Cells to Physeal Defects: An Experimental Study in Rabbits

Physeal cartilage is known to have poor self-repair capacity after injury. Evaluation of the ability of cultured mesenchymal stem cells to repair damaged physis is the topic of current research. In 10 immature New Zealand white rabbits autogenous mesenchymal stem cells were transplanted into a iatrogenic physeal defect in a lateral portion of the distal growth plate of the right femur. The same defect without stem cells transplantation in the left femoral distal physis served as a control. In our study, we used our own technique of implantation of MSCs with a newly modified gel scaffold (New Composite Hyaluronate/Collagen Type I/Fibrin Scaffold). The rabbits were euthanized 4 months after transplantation. Bone length discrepancy and valgus deformity were measured from femoral radiographs. Healing of the defect was investigated histologically. The ability of mesenchymal stem cells to survive and promote cartilage healing in the physeal defect was assessed by immunofluorescence. Average difference in femur length measured from surgery to euthanasia (4 months) was 0.61 ± 0.19 cm after preventive transplantation of MSCs in the right femur, but only 0.11 ± 0.07 cm in the left femur. Average angular (valgus) deformity of the right femur with MSCs preventively transplanted to iatrogenically damaged distal femoral physis was 1.2 ± 0.72 °. Valgus deformity in the left femur was 5.4 ± 2.5 °. Prophylactic transplantation of autogenous mesenchymal stem cells to iatrogenically damaged distal growth plate of the rabbit femur prevented a bone bridge formation and resulted in healing of the physeal defect with hyaline cartilage. Immunofluorescence examination showed that the chondrocytes newly formed in growth zone are the result of implanted MSCs differentiation. Femur growth in traumatized physis was maintained even after transplantation of autogenous MSCs. As compared with the opposite femur (with physeal defect but without transplanted MSCs), the bone showed no significant shortening or valgus deformity (p = 0.018)

Chondrocytic Potential of Allogenic Mesenchymal Stem Cells Transplanted without Immunosuppression to Regenerate Physeal Defect in Rabbits

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 a defect in the distal femoral physis in rabbits without the use of immunosuppressive therapy. A iatrogenic defect was created in the lateral femoral condyle of thirty-two New Zealand white rabbits, 7 weeks old, weighing 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 (three weeks and four months after implantation) and also histologically, by Pearl’s reaction and with immunofluorescence (four months after implantation). The results were compared with the data for the control defects (without stem cell implantation) in left distal femoral physes. On average, right femurs with a damaged distal physis and transplanted MSCs grew more in length (0.55 ± 0.21 cm) compared with left femurs with a physeal defect without stem cell transplantation (0.46 ± 0.23 cm). Valgus deformity of right femurs with a physeal defect and transplanted MSCs was mild (0.2 ± 0.1 °). On the contrary, left femurs with a physeal defect without transplanted MSCs showed a 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, hyaline cartilage had formed throughout the defects treated with allogenic MSCs. Labelled mesenchymal stem cells/differentiated chondrocytes were detected in the physeal defects based on magnetic resonance imaging and immunofluorescence. 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

Biomaterials and Stem Cells in the Treatment of Articular Cartilage, Meniscal, Physeal, Bone, Ligamentous and Tendineous Defects

This review briefly summarizes existing results and main trends in experimental studies dealing with the possibilities of the use of biomaterials and mesenchymal stem cells in the treatment of diseases affecting tissues derived from the mesoderm, i.e. articular cartilage, meniscus, physis, bone, ligaments and tendons. The aim of these experimental studies is to find optimal forms of treatment of the diseases of individual parts of the musculoskeletal system using methods of tissue engineering with the use of stem cell transplantation