Comparison of Preventive and Therapeutic Transplantations of Allogeneic Mesenchymal Stem Cells in Healing of the Distal Femoral Growth Plate Cartilage Defects in Miniature Pigs

Abstract

The aim of the study was to verify whether there is a difference in the lengthwise growth of the femurs and in their angular deformity when comparing preventive vs. therapeutic transplantation of allogeneic mesenchymal stem cells (MSCs) to an iatrogenic defect in the distal physis of femur. Modified composite chitosan/collagen type I scaffold with MSCs was transplanted to an iatrogenically created defect of the growth cartilage in the lateral condyle of the left femur in 20 miniature male pigs. In Group A of animals (n = 10) allogeneic MSCs were transplanted immediately after creating the defect in the distal physis of femur (preventive transplantation). In Group B of animals (n = 10) the same defect of the growth cartilage was treated by transplantation of allogeneic MSCs four weeks after its creation (therapeutic transplantation), after the excision of the bone bridge that had formed in it. On average, left femurs with a damaged distal physis and preventively transplanted allogeneic MSCs (Group A) grew during 4 months from transplantation by 0.56 ± 0.44 cm more than right femurs without the transplantation of MSCs, whereas left femurs with physeal defects treated with a therapeutic transplantation of allogeneic MSCs (Group B) by 0.14 ± 0.72 cm only, compared to right femurs without transplanted MSCs. Four months after preventive transplantation of MSCs (Group A), valgus deformity of the distal part of left femur with the defect was 0.78 ± 0.82°; in the control group (right femur in the same animal without MSCs transplantation) it was 3.7 ± 0.82°. After therapeutic transplantation of MSCs (Group B) 0.6 ± 3.4°, in the control group (right femur in the same animal without MSCs transplantation) it was 2.1 ± 2.9°. In all the animals of Groups A and B, the presence of newly formed hyaline cartilage was confirmed histologically and immunohistochemically. In the distal physis of right femurs with an iatrogenic defect of the growth cartilage without the transplantation of MSCs (control) bone bridge was formed. Preventive transplantation of allogeneic MSCs into the defect of the distal growth zone of femur appears more suitable compared to the therapeutic transplantation, with regard to the more pronounced lengthwise bone growth. Differences found in the extent of valgus deformity were non-significant comparing preventive and therapeutic transplantations of MSCs.