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

Organogenetic tolerance

“…We have shown that glucose tolerance can be normalized in streptozotocin (STZ)-diabetic (type 1) LEW [10][11][12] Intact porcine islets do not engraft following renal subcapsular implantation. However, a population of cells originating from donor islets with b-cell morphology that express insulin and porcine proinsulin mRNA engraft in kidneys of rats transplanted previously with E28 pig embryonic pancreas.…”

“…3F) porcine proinsulin mRNA engraft in host mesentery, mesenteric lymph nodes, liver and pancreas post-transplantation. [10][11][12][13] Cells originating from E28 pig pancreatic primordia engraft similarly in non immune-suppressed STZ-diabetic rhesus macaques. 3 Glucose tolerance can be nearly normalized in non-immunesuppressed diabetic rhesus macaques following transplantation of E28 pig pancreatic primordia (Fig.…”

“…LEW rats transplanted with E28 pig pancreatic primordia retain reactivity to other porcine xenoantigens (E28 pig renal primordia are rejected) 11 . Thus, our findings are consistent with induction of specific tolerance 17 to a cell component (either b cells or a stem convergence of endocrine and intestinal contents at this site may explain the link between an autoimmune pathogenesis for type 1 diabetes and environmental provocation.…”

“…Induction of organogenetic tolerance for endocrine pancreas is critically dependent on the methodology employed to transplant pig pancreatic primordia. 3,[10][11][12][13]18,19 The phenomenon may be applicable to other organs with appropriate modifications in techniques used for implantation. For example, adaptations in methodology used to xenotransplant embryonic pig kidneys 11 so as to result in engraftment that recapitulates the pattern observed following xenotransplantation of embryonic pancreas (i.e., renal cells engrafted in mesenteric lymph nodes) could render hosts tolerant to the embryonic kidney tissue and also to cells originating from adult kidneys from the same donor species.…”

Inhibition of Gamma-Secretase Activity Promotes Differentiation of Embryonic Pancreatic Precursor Cells into Functional Islet-like Clusters in Poly(Ethylene Glycol) Hydrogel Culture

“…In vivo studies involving human, porcine, and rat fetal pancreatic tissue have successfully corrected hyperglycemia in animal models of diabetes. [3][4][5][6][7] However, mechanisms to promote the in vitro differentiation of pancreatic precursor cells into a uniform population of functional beta cells have not been achieved. Additional research has focused on developing a Pdx-1þ cell population from embryonic stem cells, with the belief that properly forming and functioning islets must be generated through a cell type indistinguishable from those found in the developing pancreatic bud.…”