Islet-derived progenitors as a source of in vitro islet regeneration.
Current therapies do not prevent the complications of diabetes. Furthermore, these therapies do not address the underlying pathology; the lack of functional beta-cell mass that occurs in both types 1 and 2 diabetes. While pancreas and islet transplantation do serve to increase beta-cell mass, a lack of donor organs limits the therapeutic potential of these treatments. As such, expansion of beta-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. One potential source of islet progenitors is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. We have developed a tissue culture platform whereby isolated adult human pancreatic islets form proliferative duct-like structures expressing ductal and progenitor markers. Short-term treatment with a peptide fragment of islet neogenesis-associated protein (INGAP) induces these structures to reform islet-like structures that resemble freshly isolated islets with respect to the frequency and distribution of the four endocrine cell types, islet gene expression and hormone production, insulin content, and glucose-responsive insulin secretion. As such, the plasticity of adult human islets has significant implications for islet regeneration.
Hanley
Stephen
S
Department of Surgery, and Centre for Pancreatic Diseases, McGill University Health Centre, Montreal, Quebec, Canada.
Rosenberg
Lawrence
L
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000166:cytology* / Q000502:physiology*; D000073718:Pancreatitis-Associated Proteins; D051381:Rats; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D016610:Tissue Embedding; D023822:Tissue Engineering / Q000379:methods*