Generation of mesothelial progenitor‐like cells from mouse‐induced pluripotent stem cells

Abstract

Mesothelial cells, which cover the surface of visceral organs and serous cavities in mammals, play a crucial role in preventing adhesion. We previously reported that primary mesothelial progenitor cells (MPCs) can not only prevent postoperative adhesion but also promote liver regeneration after hepatectomy. Induced pluripotent stem cells (iPSCs) have the potential to be used for regenerative medicine. Here, we have established a differentiation protocol for mouse iPSC‐derived MPCs (miMPCs) via the exposure to defined factors, as well as purification using MPC‐specific cell surface antigens. Furthermore, the miMPCs had the ability to suppress postoperative adhesion and facilitate liver regeneration. This is the first report highlighting the generation of functional miMPCs, which may offer potential for de novo cell therapy.

Suspension culture promotes serosal mesothelial development in human intestinal organoids

“…We found that HIO serosa formation begins after day 7 of culture and is complete between days 14 and 28. Using this developmental timeline, we applied activators and inhibitors of major signaling pathways known to be involved in mesothelial differentiation or intestinal mesoderm development (Colunga et al, 2019;Dixit et al, 2013;Inagaki et al, 2019;Kolterud et al, 2009;Kruithof et al, 2006;Schlueter et al, 2006;Tian et al, 2015;VanDussen et al, 2012;Verzi and Shivdasani, 2008) using suspension HIOs and assessed their effects on the serosa.…”

Mechanisms of Peritoneal Mesothelial Cells in Peritoneal Adhesion

“…The visceral and parietal peritoneum surround the peritoneal cavity [ 19 ]. The peritoneum is covered by a thin layer of mesothelial cells [ 7 , 20 ]. Below the mesothelial cells, the basement membrane and interstitial subcutaneous tissue, including collagen fibers, blood vessels, and fibroblasts, are found [ 21 , 22 ].…”

“…The glycocalyx, composed of surfactants, phospholipids, and glycosaminoglycans distributed on top of the microvilli of PMCs, creates a lubricating environment for visceral organ activities [ 20 , 29 , 30 ]. PMCs have epithelial and mesenchymal features and can transform under physiological and pathological conditions [ 6 ].…”

“…Smooth and intact PMCs can prevent the formation of PAs; in contrast, damaged PMCs or the shedding of PMCs may be the basis for the initiation of PAs ( Figure 1 A) [ 2 , 17 , 20 ]. A mouse model of PAs, induced by ligation or rubbing, suggested that PMCs with high mesothelin expression after injury may induce genes that regulate cell differentiation and proliferation, allowing PMCs to break away from the basement membrane and enter the peritoneal cavity to initiate PAs.…”