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Gamma-irradiation as a tool to reduce immunogenicity of islet allo- and xenografts
Sensitivity of pancreatic endocrine cells to gamma-irradiation and alteration of islet immunogenicity by irradiation were examined. Syngeneic, allogeneic (DBA/2) and xenogeneic (rat) islets were irradiated and transplanted at varying doses (8, 24, 40, 80 and 160 Gy) into streptozotocin-induced diabetic B6AF1 mice. In an isograft model, late loss of graft function was observed in some animals given 200 24-Gy-irradiated islets. However, larger numbers (400-500) of islets given 40 Gy irradiation did not show reversal of normoglycemia. With higher doses (80 or 160 Gy) significant early as well as late graft loss was observed. In an allograft model, the irradiated islet allografts survived beyond controls. Marked prolongation was achieved with a broad range of irradiation doses between 8 Gy and 120 Gy with 30-90% of recipients maintaining normoglycemia over 50 days. Late loss of graft function was observed between 78 and 180 days with a dose over 24 Gy. Increasing dose resulted in a better allograft survival rate in the early postoperative period, but tended to curtail longterm survival. In an xenograft model, irradiation of islets with 8 to 24 Gy led to prolongation of graft survival. Maximum graft prolongation was achieved with 24 Gy. Higher doses were much less effective and, in some recipients, caused shortening of graft survival.(ABSTRACT TRUNCATED AT 250 WORDS)
Sensitivity of pancreatic endocrine cells to gamma-irradiation and alteration of islet immunogenicity by irradiation were examined. Syngeneic, allogeneic (DBA/2) and xenogeneic (rat) islets were irradiated and transplanted at varying doses (8, 24, 40, 80 and 160 Gy) into streptozotocin-induced diabetic B6AF1 mice. In an isograft model, late loss of graft function was observed in some animals given 200 24-Gy-irradiated islets. However, larger numbers (400-500) of islets given 40 Gy irradiation did not show reversal of normoglycemia. With higher doses (80 or 160 Gy) significant early as well as late graft loss was observed. In an allograft model, the irradiated islet allografts survived beyond controls. Marked prolongation was achieved with a broad range of irradiation doses between 8 Gy and 120 Gy with 30-90% of recipients maintaining normoglycemia over 50 days. Late loss of graft function was observed between 78 and 180 days with a dose over 24 Gy. Increasing dose resulted in a better allograft survival rate in the early postoperative period, but tended to curtail longterm survival. In an xenograft model, irradiation of islets with 8 to 24 Gy led to prolongation of graft survival. Maximum graft prolongation was achieved with 24 Gy. Higher doses were much less effective and, in some recipients, caused shortening of graft survival.(ABSTRACT TRUNCATED AT 250 WORDS)