Trophic factors from pancreatic islets in combined hepatocyte-islet allografts enhance hepatocellular survival.
The purpose of this study was to determine the effect of pancreatic islets on the survival of clusters of rat hepatocytes transplanted across a major histocompatibility barrier into an ectopic site. Aggregates of hepatocytes and pancreatic islets were obtained from Wistar-Furth rats by an automated method of collagenase digestion. Approximately 8000 Wistar-Furth hepatocyte clusters (100 to 300 micron diameter) were transplanted beneath the renal capsule of Lewis rats with or without the addition of 800 pancreatic islets. Recipients received subcutaneous injections of cyclosporine A (CsA): 30 mg/kg on days 0, 1, and 2, 10 mg/kg on days 3 to 7, and 10 mg/kg every other day for days 8 to 28. In the absence of CsA recipient treatment, all the allografts were rejected within 7 days. The combined hepatocyte-islet allografts in recipients treated with CsA showed maintenance of morphologic integrity of both hepatocytes and islet cells 1, 2, and 4 weeks after transplantation, whereas in the absence of pancreatic islets, the hepatocellular aggregates degenerated despite CsA treatment, leaving only a thin rim of hepatocytes immediately adjacent to the renal parenchyma. It can be concluded that in immunosuppressed recipients hepatocyte-islet renal subcapsular allografts survived despite the presence of an intact liver, which indicates a possible role of trophic factors released locally from the islets.
Ricordi
C
C
Department of Surgery, San Raffaele Institute, Milan, Italy.
Lacy
P E
PE
Callery
M P
MP
Park
P W
PW
Flye
M W
MW
D000818:Animals; D003524:Cyclosporins / Q000008:administration & dosage; D006085:Graft Survival; D006649:Histocompatibility Antigens; D007515:Islets of Langerhans / Q000648:ultrastructure; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000601:surgery; D008099:Liver / Q000648:ultrastructure; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D014181:Transplantation Immunology; D014185:Transplantation, Isogeneic
D003524:Cyclosporins; D006649:Histocompatibility Antigens