The effect of transgenic expression of TGF-beta1 on transplanted islet graft survival.

Background/Aims: Transgenic mice expressing the active form of porcine TGF-β1 (NOD- TGF-β1 Tg) were completely protected from autoimmune diabetes in the NOD genetic background in our previous study. Here, we attempted to determine whether transgenic expression of TGF-β1 in transplanted islets prevents autoimmune destruction in NOD mice. Methodology: We transplanted islets to the subcapsular region of the kidney using NOD-TGF-β1 Tg and NOD mice as donor and recipient or vice versa. Cyclophosphamide was administered twice to streptozocin-induced diabetic females NOD-TGF-β1 Tg or their female littermates after islet transplantation. Results: All islets grafts of NOD-TGF-β1 Tg in spontaneously diabetic NOD mice were rejected earlier than those of their littermates. Hyperglycemia was induced in all littermates, but three out of four NOD-TGF-β1 Tg, which were STZ-induced diabetic female mice, remained normoglycemic in response to the administration of cyclophosphamide after islet transplantation. Conclusions: Our results lack direct evidence for the local paracrine TGF-β1 to protect the transplanted islet grafts. We observed, however, prolonged survival of NOD islets grafts in diabetic NOD-TGF-β1 Tg suggesting the protective role of transgenic TGF-β1 to suppress the autoimmune process in our syngenic transplantation model. We are convinced that this data could help resolve many problems regarding islet transplantation for type 1 diabetes.