The effect of transgenic expression of TGF-beta1 on transplanted islet graft survival.
OBJECTIVE
Transgenic mice expressing the active form of porcine TGF-beta1 (NOD- TGF-beta1 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-beta1 in transplanted islets prevents autoimmune destruction in NOD mice.


METHODS
We transplanted islets to the subcapsular region of the kidney using NOD-TGF-beta1 Tg and NOD mice as donor and recipient or vice versa. Cyclophosphamide was administered twice to streptozocin-induced diabetic females NOD-TGF-beta1 Tg or their female littermates after islet transplantation.


RESULTS
All islets grafts of NOD-TGF-beta1 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-beta1 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-beta1 to protect the transplanted islet grafts. We observed, however, prolonged survival of NOD islets grafts in diabetic NOD-TGF-beta1 Tg suggesting the protective role of transgenic TGF-beta1 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.
Yamasaki
Seiji
S
Department of Surgery, Institute of Health Bioscience, The University of Tokushima Graduate School, 3-18-15 Kuramoto Tokushima 770-8501, Japan.
Kurita
Nobuhiro
N
Hata
Jun-ichi
J
Moritani
Maki
M
Itakura
Mitsuo
M
Shimada
Mitsuo
M
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics; D003520:Cyclophosphamide / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000628:therapy; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D019076:Transgenes
D053773:Transforming Growth Factor beta1; D003520:Cyclophosphamide