Effect of immunosuppression on survival and growth of cartilage produced by transplanted allogeneic epiphyseal chondrocytes.

Strong short-term immunosuppression improved survival of cartilage formed by transplanted allogeneic epiphyseal chondrocytes in mice. The agents tested were cortisone acetate (CA), cyclophosphamide (CY), procarbazine (PCH), and antithymocyte serum (ATS). Their effect on syngeneic grafts was examined morphologically and histomorphometrically. In untreated recipients, chondrocytes formed cartilage nodules that underwent endochondral ossification. Except for high repetitive doses of CY, none of the other agents interfered with normal cartilage formation. However, all agents affected endochondral ossification. In the allogeneic system, the effect of immunosuppression was examined morphologically and by evaluation of specific humoral and cellular antigraft immunity. Allogeneic chondrocytes evoked a strong immune response in untreated mice, and cartilage was gradually destroyed by infiltrating cells. Endochondral ossification did not occur in this system. Neither agent given alone exerted a marked, long-lasting protective effect upon the graft. However, combined treatment with ATS and PCH inhibited immune response and completely prevented infiltrate formation and allowed endochondral ossification similar to that in the syngeneic control. Although some weak signs of antigraft immunity were seen after six weeks, it is possible that they were due to secondary exposure of antigen-bearing chondrocytes in the course of endochondral ossification.