Endocrine Abstracts (2006) 11 P333

Adult pancreatic islet progenitor cells exhibit plasticity in vitro

WE Leadbeater1, MR Summerfield1, DJ Hill2, M Berry1 & A Logan1

1University of Birmingham, Birmingham, United Kingdom; 2Lawson Health Research Institute, London, Ontario, Canada.

Adult progenitor cells exist in most adult tissues, their differentiation being primed by insult, repopulating damaged or dysfunctional tissue. Utilisation of resident progenitor cells has the potential to cure many diseases, including neurodegenerative disorders or diabetes which presently can only be managed. This potential is limited in the brain by constraints on endogenous progenitor cell mobilisation and by difficulties in progenitor cell harvesting for ex vivo expansion and differentiation. The regenerative capacity of progenitors is dependent on both their phenotype and microenvironment, and their plasticity may allow cross-tissue transplantation. Since adult pancreatic endocrine and neural progenitors share similarities in lineage gene expression and developmental pathways, we hypothesise that, given neural environmental conditions, cultured pancreatic progenitors will expand and differentiate along neuronal lineages. We have shown that adult mouse pancreatic islets contain resident progenitor cell populations that can be isolated, cultured and characterised by immunolocalisation of the stem cell markers c-kit and CD34. Mouse pancreatic islets were isolated by collagenase digestion and dextran gradient separation. The cell preparation consisted of 90% or better dithizone-positive islets. The prepared islets were embedded in rat tail collagen and cultured in DMEM/F12, cholera toxin and EGF to develop expanded epithelial monolayers enriched with c-kit, nestin, c-Met and CD34 positive cells after 4 weeks in culture. When prepared pancreatic islets were cultured on poly-L-ornithine/laminin coated plates in DMEM/F12, N2 supplement, glucose and FGF-2 (a neural environment), they also formed a monolayer and within three weeks the cells had differentiated into multiple phenotypes including neuron-like cells, as defined by neurofilament immunoreactivity. We conclude that pancreatic islets have the capacity to differentiate into multiple cell types that are dependent on the environment, not the tissue of origin. Given the correct stimuli, pancreatic islet progenitor cells in vitro exhibit plasticity and the ability to differentiate along neuronal lineages.

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