Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets

Generation and expansion of multipotent mesenchymal progenitor cells from cultured human pancreatic islets

“…Fibroblast-like cells emerging from pancreatic islets have been shown to be able to differentiate into insulin-expressing cells. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] To evaluate the ability of hPIDM cells to differentiate into a pancreatic endocrine phenotype, cells were cultured for 21 days in a medium for endocrine differentiation. Under these conditions, cells formed clusters that remained adherent to culture plates for the first week, but afterward detached acquiring an isletlike morphology (Figure 6a).…”

“…As shown in Figure 7, all 26 Immortalized mesenchymal cells derived from human pancreatic islets were reported not only to differentiate into hepatocytes and different mesenchymal cell lineages, but also to form insulin-expressing cells. 12 In contrast, very recent reports from several laboratories have reported on studies based on genetic lineage tracing in mice that seem to rule out the possibility that b-cells could undergo an epithelial to mesenchymal transition, thus suggesting that the cell population obtained from cultures of pancreatic islets may originate from preexisting mesenchymal cells. [27][28][29][30] Similar conclusions were obtained in experiments performed with transgenic mice expressing the green fluorescent protein (GFP) selectively in b-cells.…”

“…6 Additional studies suggested that progenitor cells may reside within the pancreatic ductal epithelium 2-7 or in the acinar tissue. 8,9 Nevertheless, the exact nature and localization of adult pancreatic stem/ progenitor cells remains controversial [9][10][11][12][13][14][15][16] and their existence in vivo, at least in mice, has recently been questioned. 6 Recent evidence has shown that human embryonic stem cells are able to differentiate into insulin-producing cells in vitro, thus potentially leading to an unlimited source of cells for transplantation.…”

“…17,18 Some of these studies have noted that cultured islet cells may express nestin, an intermediate filament expressed in several precursor/stem cells. [10][11][12] The association of nestin-positive cells with human pancreatic islets is of interest in light of evidence that nestin expression precedes the appearance of b-cells during embryogenesis. 13 In addition, although no direct origin of b-cells from nestinpositive cells has been demonstrated in postnatal life, 14 recent reports have shown that nestin-positive progenitor cells isolated from human fetal pancreas may have phenotypic markers identical to mesenchymal stem cells and are able to proliferate and differentiate into insulin-producing cells in vitro.…”

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

“…Pancreasderived MSCs cultured for 21 days in a medium for endocrine differentiation formed clusters that acquiring an islet-like morphology and secreted insulin in response to glucose stimulation (Zanini et al 2011). Eberhardt et al (2006) isolated nestin-positive MSCs from human pancreatic islets and immortalized them with lentiviral vectors coding telomerase and mBmi. Immortalized cells were differentiated into islet-like clusters.…”