Effect of various immunosuppressive monotherapies on survival and histopathology of monkey islet xenografts in rats.
BACKGROUND
The isolation and testing of monkey islets after transplantation in small animal models provides basic information about their functional capacity. We describe the effect of cyclosporine A (CsA), tacrolimus (FK506) or prednisolone monotherapy on preventing monkey islet graft rejection after xenoTx in a rat model. Histopathological aspects are reported.


METHODS
Indian bonnet monkey (Macaca radiata radiata) islets were isolated by a simple stationary digestion technique using collagenase. The islets were purified with dextran density gradients and were transplanted under the renal capsule of normal or diabetic rats. The rats received a daily dose of CsA, or FK506, or prednisolone, and the grafts were removed at different intervals to determine islet survival. The effect of discontinuation of CsA on islet graft survival was also monitored. Histological examination of islets transplanted into normal or streptozotocin-induced diabetic rats was carried out. In diabetic rats, islet survival was determined by the graft's ability to achieve euglycemia.


RESULTS
Reversal of diabetes was achieved in all transplanted diabetic rats, demonstrating the efficacy of the isolated monkey islets. Histological examination indicated that monkey islets survived in the presence of continuous high-dose immunosuppressive monotherapy in rats. Various types of infiltrating cells were observed in the grafted area at varying times after transplantation, depending on the immunosuppressive treatment. After discontinuation of CsA, the grafts were protected for a short period.


CONCLUSIONS
This study provided evidence for monkey islet survival after transplantation into rats receiving immunosuppressive monotherapy. Basic information on infiltrating cell types may be important in the study of xenograft rejection.
Department of Physiology, Christian Medical College and Hospital, Vellore, TN, India. isletologist@hotmail.com
A N
AN
Balamurugan
Everette J R
EJ
Nelson
Banumathi
B
Ramakrishna
S
S
Gunasekaran
D000818:Animals; D001786:Blood Glucose; D016572:Cyclosporine / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000628:therapy*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods; D008255:Macaca radiata; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology; D023001:Transplantation Tolerance / Q000187:drug effects* / Q000276:immunology; D014183:Transplantation, Heterologous / Q000379:methods*
D001786:Blood Glucose; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D016559:Tacrolimus