Pancreas Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Pancreas Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

Insulin-producing cells derived from human pancreatic non-endocrine cell cultures reverse streptozotocin-induced hyperglycaemia in mice.

Zhao M, Amiel SA, Christie MR, Rela M, Heaton N, Huang GC

Department of Diabetes, Endocrinology and Internal Medicine, King's College GKT Medical School, Bessemer Road, London SE5 9PJ, UK.

AIMS/HYPOTHESIS: The aim of the study was to investigate the potential of human pancreatic non-endocrine cells to transdifferentiate into endocrine cells that would be capable of secreting insulin in response to glucose and ameliorating insulin-deficient diabetes after transplantation. MATERIALS AND METHODS: Cell fractions enriched with exocrine cells after human islet isolation were treated with streptozotocin to remove residual beta cells, grown in monolayer culture to allow de-differentiation, transferred to cluster culture for redifferentiation in the presence of activin A, betacellulin, nicotinamide and glucose, supplemented with 10% FCS, and administered to streptozotocin-induced diabetic SCID mice. A subset of cells was transfected with the IPF1 gene (also known as PDX1) before transdifferentiation. RESULTS: No insulin was detectable in cell preparations after 5 days of treatment with streptozotocin. In monolayer culture, 90% of the streptozotocin-treated pancreatic cells co-expressed cytokeratin-19 and vimentin at 2 weeks and 60% expressed nestin at 4 weeks. Cell cultures with a high proportion of nestin-expressing cells had greater plasticity for transdifferentiation into cells with phenotypic and functional markers of beta cells, this property being significantly enhanced by transfection with IPF1 gene and leading to 15+/-6.7% insulin-positive cells after transplantation vs. 0.01% of cells transplanted after streptozotocin treatment alone. These cells improved glucose control in all of 42 diabetic mice after transplantation, restoring normoglycaemia in 40%. CONCLUSIONS/INTERPRETATION: Human pancreatic cells are a potential source of new glucose-responsive insulin-producing cells that may be developed further for clinical use.

Published 10 October 2005 in Diabetologia, 48(10): 2051-61.
Full-text of this article is available online (may require subscription).

© 2005-2008 Pancreas Transplant Research Today. All Rights Reserved.