Normalization of glucose post-transplantation of pig pancreatic anlagen into non-immunosuppressed diabetic rats depends on obtaining anlagen prior to embryonic day 35

Abstract

Embryonic day (E) 28 (E28) pig pancreatic anlagen (PPA) transplanted into the omentum of non-immunosuppressed steptozotocin-diabetic Lewis rats normalize levels of circulating glucose within 2-4 weeks. Following transplantation formerly diabetic rats have porcine insulin, but no rat insulin detectable in circulation. At 3 weeks post-E28 PPA transplantation, bits of insulin-positive tissue are observed amidst host omental fat, but by 6 weeks only individual alpha and beta cells remain. In contrast, E35 PPA transplantation does not normalize glucose and 6 weeks post-implantation of E35 PPA transplanted tissue is rejected. In contrast to E28 PPA, no trace of implanted renal tissue is detectable post implantation of E28 pig renal anlagen (PRA) in non-immunosuppressed non-diabetic rats or in streptozocin-diabetic rats previously transplanted with E28 PPA. In the latter, normoglycemia is maintained post-PRA transplantation. We conclude that normalization of glucose levels following transplantation of PPA into non-immunosuppressed Lewis rats depends on obtaining the anlagen before E35 and that prior successful engraftment of E28 PPA as reflected by normalization of glucose, does not permit successful engraftment of E28 PRA.