Composite kidney-islet transplantation prevents recurrent autoimmune beta-cell destruction.
BACKGROUND
Clinically successful islet transplantation has been rare despite adequate isolation techniques. Reenactment of the original autoimmune beta-cell destruction may contribute to the poor results. Distinguishing autoimmune effects from rejection can be accomplished with isogeneic transplants exchanged between diabetes-prone (BB-DP) and diabetes-resistant (BB-DR) rats. These experiments determine the relative sensitivity of islet, whole pancreas, and composite kidney-islet transplants to recurrent autoimmunity.


METHODS
Acutely diabetic (BB-Ac) BB rats served as recipients of vascularized pancreas, intraportal (IPo) or renal capsular (KC) islet transplants, or vascularized composite kidney-islet grafts from BB-DR or BB-DP donors. Graft function was assessed by daily blood glucose level, and the outcome was confirmed on histologic examination. Cyclosporine 5 mg/kg/day intramuscularly was administered to assess its effect on recurrent beta-cell injury.


RESULTS
BB-DP pancreases developed recurrent autoimmunity in 55% of cases; cyclosporine afforded complete protection if maintained. Diabetes resistance was transplanted with 23 of 23 BB-DR pancreas grafts; however, islet isolation led to a loss of diabetes resistance for islet grafts to the KC and IPo. Cyclosporine protected KC but not IPo islets. Composite BB-DR kidney-islet transplants functioned indefinitely in all cases.


CONCLUSIONS
Transplanted islets initially survive by passive diffusion but are ultimately revascularized by capillary ingrowth. The finding that composite kidney-islet transplants function indefinitely suggests that the revascularizing endothelium may play a role in resistance or susceptibility to autoimmune beta-cell destruction.
Bartlett
S T
ST
Department of Surgery, University of Maryland Medical Systems, Baltimore 21201.
Hadley
G A
GA
Dirden
B
B
Schweitzer
E J
EJ
Eans
S
S
Pham
D
D
Sheffield
C
C
D000818:Animals; D015551:Autoimmunity; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007515:Islets of Langerhans / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D012008:Recurrence
D000949:Histocompatibility Antigens Class II