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Characterization of Myelomonocytoid Progenitor Cells with Mesenchymal Differentiation Potential Obtained by Outgrowth from Pancreas Explants

DOI: 10.1155/2012/429868

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Abstract:

Progenitor cells can be obtained by outgrowth from tissue explants during primary ex vivo tissue culture. We have isolated and characterized cells outgrown from neonatal mouse pancreatic explants. A relatively uniform population of cells showing a distinctive morphology emerged over time in culture. This population expressed monocyte/macrophage and hematopoietic markers (CD11b+ and CD45+), and some stromal-related markers (CD44+ and CD29+), but not mesenchymal stem cell (MSC)-defining markers (CD90? and CD105?) nor endothelial (CD31?) or stem cell-associated markers (CD133? and stem cell antigen-1; Sca-1?). Cells could be maintained in culture as a plastic-adherent monolayer in culture medium (MesenCult MSC) for more than 1 year. Cells spontaneously formed sphere clusters “pancreatospheres” which, however, were nonclonal. When cultured in appropriate media, cells differentiated into multiple mesenchymal lineages (fat, cartilage, and bone). Positive dithizone staining suggested that a subset of cells differentiated into insulin-producing cells. However, further studies are needed to characterize the endocrine potential of these cells. These findings indicate that a myelomonocytoid population from pancreatic explant outgrowths has mesenchymal differentiation potential. These results are in line with recent data onmonocyte-derivedmesenchymal progenitors (MOMPs). “M.-E. Roehrich passed away whilst this article was in press.” 1. Introduction The pancreas is a complex organ consisting of three principal cell types: endocrine islets, exocrine acini, and ducts. Evidence of differentiation of new β-cells from pancreatic nonislet cells suggests the existence of pancreatic nonendocrine stem/progenitor cells [1, 2]. New β-cells may also result from replication of preexisting β-cells [3], or from progenitor cells originating from the ductal epithelium [4–6] or the exocrine tissue of the pancreas [7–9]. Pancreatic progenitor cells express key transcription factors involved in the embryological development of endocrine cells such as pancreatic and duodenal homeobox factor 1 (Pdx1), neurogenin 3 (Ngn3) and paired box 4 (Pax4), or embryonic markers such as Oct-4 and Nanog, or nestin [10]. Pancreatic progenitor cells have been prospectively isolated by fluorescence-activated cell sorting (FACS) using specific antibodies that recognize cell-surface epitopes expressed by stem/progenitor cells in other tissues, such as CD133, CD117 (c-kit/stem cell factor receptor), ATP-binding cassette (ABC) G2, and mesenchymal stem cell (MSC) markers [11–15]. An alternative method for the

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