Adult Pancreas Side Population Cells Expand after beta Cell Injury and Are a Source of Insulin-Secreting Cells
- Author(s)
- Banakh, I; Gonez, LJ; Sutherland, RM; Naselli, G; Harrison, LC;
- Details
- Publication Year 2012-11-09,Volume 7,Issue #11,Page e48977
- Journal Title
- PLOS ONE
- Publication Type
- Journal Article
- Abstract
- Pancreas stem cells are a potential source of insulin-producing beta cells for the therapy of diabetes. In adult tissues the 'side population' (SP) of cells that effluxes the DNA binding dye Hoechst 33342 through ATP-binding cassette transporters has stem cell properties. We hypothesised therefore that the SP would expand in response to b cell injury and give rise to functional b cells. SP cells were flow sorted from dissociated pancreas cells of adult mice, analysed for phenotype and cultured with growth promoting and differentiation factors before analysis for hormone expression and glucose-stimulated insulin secretion. SP cell number and colony forming potential (CFP) increased significantly in models of type diabetes, and after partial pancreatectomy, in the absence of hyperglycaemia. SP cells, similar to 1% of total pancreas cells at 1 week of age, were enriched >10-fold for CFP compared to non-SP cells. Freshly isolated SP cells contained no insulin protein or RNA but expressed the homeobox transcription factor Pdx1 required for pancreas development and beta cell function. Pdx1, along with surface expression of CD326 (Ep-Cam), was a marker of the colony forming and proliferation potential of SP cells. In serum-free medium with defined factors, SP cells proliferated and differentiated into islet hormone-expressing cells that secreted insulin in response to glucose. Insulin expression was maintained when tissue was transplanted within vascularised chambers into diabetic mice. SP cells in the adult pancreas expand in response to beta cell injury and are a source of beta cell progenitors with potential for the treatment of diabetes. Citation: Banakh I, Gonez LJ, Sutherland RM, Naselli G, Harrison LC (2012) Adult Pancreas Side Population Cells Expand after beta Cell Injury and Are a Source of Insulin-Secreting Cells. PLoS ONE 7(11): e48977. doi:10.1371/journal.pone.0048977
- Publisher
- PUBLIC LIBRARY SCIENCE
- Keywords
- EMBRYONIC STEM-CELLS; PROGENITOR CELLS; ISLET TRANSPLANTATION; MOUSE PANCREAS; IN-VIVO; REGENERATION; PHENOTYPE; SURFACE; DIFFERENTIATION; MAINTENANCE
- Research Division(s)
- Molecular Medicine; Immunology
- Publisher's Version
- https://doi.org/10.1371/journal.pone.0048977
- Open Access at Publisher's Site
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- © 2012 Banakh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creation Date: 2012-11-09 12:00:00