Identification of pancreatic stellate cell population with properties of progenitor cells: new role for stellate cells in pancreas
Résumé
Numerous studies conducted in a diversity of adult tissues have reported that certain stem cells are characterized by the expression of a protein known as the ABCG2 transporter. In the adult pancreas, various multipotent progenitors have been proposed, however the ABCG2 marker has only been detected in the so-called Side Population. In the present study we aim to identify new ABCG2+ pancreatic cell populations and to explore whether they exhibit properties of progenitor cells. We isolated and expanded mitoxantrone-resistant cells from pancreata of lactating rats by drug selection. These cells were characterized and maintained in different stages of differentiation using several cocktail media plus matrigel. Differentiation was assessed by RT-PCR, immunocytochemistry, electron microscopy and ELISA methods. The expanded cell population demonstrated a phenotype of pancreatic stellate cells (PaSC). Spontaneous cell clusters occurred during cell expansion and they showed weak expression of Pdx-1. Moreover, the presence of inductive factors in the Matrigel plus exendin-4 led to an increase in Pdx-1 and endocrine genes, such as insulin, IAPP, glucagon, GLUT2, chromogranin A, and convertases PC1/3, PC2 were also detected. Immunocytochemical analysis showed co-localization of insulin and c-peptide, while ultrastructural studies revealed the presence of granules. Insulin secretion of cell clusters was detected in the cell culture medium. We have identified a population of PaSCs, which express the ABCG2+ transporter and have the capacity to transdifferentiate into insulin producing-cells. Although the potential therapeutic application remains to be tested, PaSCs could represent a future option in the research of insulin replacement in diabetes.
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