Accession Number : ADA549716


Title :   Endocrine Pancreas Regeneration


Descriptive Note : Final rept. 1 Jun 2006-31 May 2010


Corporate Author : CHILDREN'S HOSPITAL OF PITTSBURGH PA


Personal Author(s) : Trucco, Massimo


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a549716.pdf


Report Date : Jun 2010


Pagination or Media Count : 194


Abstract : Type 1 diabetes is considered an autoimmune disease characterized by the presence of inflammatory cells in the islets of Langerhans. These cells are T lymphocytes, considered responsible for the destruction of the insulin producing beta-cells present in the islets. When the majority of the beta cells are dead, the disease presents, frequently with an abrupt and clinically serious onset. Hyperglycemia can be induced by chemical destruction of the insulin producing beta cells in monkeys. Following diabetes induction, histological examination of the pancreas shows islet cells with virtually null or sporadic immuno-reactivity for insulin. In our pilot studies, monkeys (macaca fascicularis) were rendered diabetic prior to receiving a xenogeneic porcine islet transplantation. A recovery of endogenous C-peptide production was observed in monkey recipients of steadily functioning pig islet grafts, concurrently to improved metabolic control. Histological analysis of the pancreatic tissue of these monkeys showed: increased proliferative (Ki67+) activity in the pancreas; small aggregates of insulin positive cells detached from the pre-existing?damaged islets; as well as high numbers of CK19+ cells that also showed strong insulin positive immunoreactivity. Such hallmarks were not seen in diabetic animals kept under insulin daily administrations, nor in recipients that experienced early graft loss. It remains to be demonstrated whether islet cell transplantation, in combination with a regimen of a non-diabetogenic immunosuppression, has a role in triggering endogenous insulin production.


Descriptors :   *AUTOIMMUNE DISEASES , *DIABETES , *INFLAMMATION , *INSULIN , *PANCREAS , *STEM CELLS , DAILY OCCURRENCE , DISEASES , ENDOCRINE GLANDS , HISTOLOGICAL TECHNIQUES , HISTOLOGY , HYPERGLYCEMIA , INDUCTION SYSTEMS , MACACA FASCICULARIS , METABOLISM , PILOT STUDIES , SURGICAL TRANSPLANTATION , SWINE , T LYMPHOCYTES


Subject Categories : Biochemistry
      Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE