Growing new endocrine pancreas in situ.
Type 1 diabetes mellitus is a major cause of endstage renal disease in young adults. Maintenance of normoglycemia in type 1 diabetics using exogenous insulin is difficult under the best of circumstances. Transplantation therapies are limited by the scarcity of human donor organs, rendering a priority the identification of an alternative source for replacing insulin-secreting cells. Embryonic pancreatic primordia transplanted into diabetic animal hosts undergo selective endocrine differentiation in situ and normalize glucose tolerance. Pancreatic primordia can be transplanted across isogeneic, allogeneic, and both concordant (rat-to-mouse) and highly disparate (pig-to-rodent) xenogeneic barriers. Successful transplantation of pancreatic primordia depends on obtaining them at defined windows during embryonic development within which the risk of teratogenicity is eliminated, growth potential is maximized, and immunogenicity is reduced. Here we review studies exploring the potential for pancreatic organogenesis post-transplantation of embryonic primordia as a therapy for type 1 diabetes.
Hammerman
Marc R
MR
Renal Division, Box 8126, Department of Medicine, and Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA. mhammerm@wustl.edu
D000818:Animals; D017690:Cell Transplantation / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D006801:Humans; D038081:Organogenesis; D010179:Pancreas / Q000033:anatomy & histology / Q000196:embryology* / Q000254:growth & development; D019397:Pancreas, Artificial; D023822:Tissue Engineering / Q000379:methods*