Generation of functional mesothelial cells from human iPSCs that restore peritoneal integrity in experimental peritoneal injury

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Long-term peritoneal injury results in loss of mesothelial integrity and impaired ultrafiltration, limiting the durability of peritoneal dialysis. Because primary human peritoneal mesothelial cells (PMCs) are difficult to obtain and expand, regenerative strategies for restoring peritoneal function have remained limited. Methods We developed a protocol to differentiate human induced pluripotent stem cells (iPSCs) into functional peritoneal mesothelial-like cells (iPMCs). The molecular and functional characteristics of iPMCs were evaluated using gene expression analyses and functional assays, including comparison with a mesothelial cell model. The therapeutic effect of iPMCs was evaluated in a methylglyoxal-induced experimental peritoneal injury mouse model. Results iPMCs exhibited typical cobblestone morphology and expressed key mesothelial markers including CK18, WT1 and MSLN. Transcriptomic analysis demonstrated strong similarity between iPMCs and primary PMCs. In vivo, intraperitoneal administration of iPMCs partially improved peritoneal transport parameters in a mouse model of peritoneal injury. Conclusions We successfully generated functional mesothelial cells from human iPSCs that reproduce mesothelial-like functional properties and suggest potential for restoring peritoneal integrity. This study demonstrates the feasibility of iPSC-derived mesothelial cells as

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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