Differentiation of biologically functional peritoneal mesothelial cells from human induced pluripotent stem cells

Abstract

Abstract The peritoneum, which provides a slippery, nonadhesive, and protective surface for body cavities and internal organs, comprises peritoneal mesothelial cells (PMCs). Peritoneum is semipermeable, which makes it useful for performing peritoneal dialysis, but prolonged exposure to dialysate causes peritoneal adhesions. PMC replenishment could help treat adhesions in patients undergoing peritoneal dialysis; however, it is difficult to obtain a sufficient yields of PMCs to achieve this. Here, we developed a method for differentiating PMCs from human induced pluripotent stem cells (hiPSCs). The hiPSCs were initially differentiated to the intermediate lateral plate mesoderm (LPM) stage in the presence of FGF2 and BMP4. The LPM-stage cells were then differentiated into PMCs by activation of Wnt and retinoic acid signaling pathways and BMP inhibition. Expression of PMC markers verified correct cellular differentiation. Passaging of the induced PMCs (iPMCs) resulted in a uniform population of mature cells that were permeable to small molecules but only exhibited low permeability for large molecules. In addition, the iPMCs appeared to have regenerative and restorative properties. These findings suggest that iPMCs could help study human peritoneal function and be used for cell therapy in patients undergoing peritoneal dialysis.