Abstract
BackgroundInduced pluripotent stem cells (iPSCs) can generate epithelial stem cells (EpSCs) as seed cells for skin substitutes to repair skin defects. Here, we investigated the effects of a human acellular amniotic membrane (hAAM) combined with iPSC-derived CD200+/ITGA6+ EpSCs as a skin substitute on repairing skin defects in nude mice.MethodsHuman urinary cells isolated from a healthy donor were reprogrammed into iPSCs and then induced into CD200+/ITGA6+ epithelial stem cells. Immunocytochemistry and RT-PCR were used to examine the characteristics of the induced epithelial stem cells. iPSC-derived EpSCs were cultured on a hAAM, and cytocompatibility of the composite was analyzed by CCK8 assays and scanning electron microscopy. Then, hAAMs combined with iPSC-derived EpSCs were transplanted onto skin defects of mice. The effects of this composite on skin repair were evaluated by immunohistochemistry.ResultsThe results showed that CD200+/ITGA6+ epithelial stem cells induced from iPSCs displayed the phenotypes of hair follicle stem cells. After seeding on the hAAM, iPSC-derived epithelial stem cells had the ability to proliferate. After transplantation, CD200+/ITGA6+ epithelial stem cells on the hAAM promoted the construction of hair follicles and interfollicular epidermis.ConclusionsThese results indicated that transplantation of a hAAM combined with iPS-derived EpSCs is feasible to reconstruct skin and skin appendages, and may be a substantial reference for iPSC-based therapy for skin defects.
Highlights
Induced pluripotent stem cells can generate epithelial stem cells (EpSCs) as seed cells for skin substitutes to repair skin defects
Generation and characterization of Induced pluripotent stem cells (iPSCs) iPSCs were generated from urinary cells using EBNA1based episomal vectors
These results indicated that pluripotent stem cells with specific gene expression and differentiation pluripotency resembling those of embryonic stem cells had been established
Summary
Induced pluripotent stem cells (iPSCs) can generate epithelial stem cells (EpSCs) as seed cells for skin substitutes to repair skin defects. We investigated the effects of a human acellular amniotic membrane (hAAM) combined with iPSC-derived CD200+/ITGA6+ EpSCs as a skin substitute on repairing skin defects in nude mice. Skin is the largest organ of the human body and the barrier between internal and external environments. Because skin is located at the surface of the human body, it is vulnerable to injury. More than 70 million people suffer from skin defects and require surgical treatment [1], resulting in significant medical costs [2]. Cells with more potential to construct a skin substitute remain to be discovered
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