Feasibility of repairing full-thickness skin defects by iPSC-derived epithelial stem cells seeded on a human acellular amniotic membrane

  • Stem Cell Res Ther. 2019 May 31;10(1):155. doi: 10.1186/s13287-019-1234-9.
Huateng Zhou  1 ,  Lixiang Wang  2 ,  Cui Zhang  3 ,  Jintao Hu  1 ,  Jianlin Chen  3 ,  Weibin Du  2 ,  Fei Liu  4 ,  Weifan Ren  1 ,  Jinfu Wang  5 ,  Renfu Quan  6
Affiliations
  • 1. Clinical Medical College, Zhejiang Chinese Medical University, Zhejiang, 310053, Hangzhou, China.
  • 2. Department of Orthopedic Surgery, Xiaoshan Traditional Chinese Medical Hospital, Zhejiang, 311200, Hangzhou, China.
  • 3. Laboratory of Stem Cells, Institute of Cell Biology, College of Life Sciences, Zhejiang University, Zhejiang, 310058, Hangzhou, China.
  • 4. Department of Chinese Medicine Rehabilitation, Xiushan People's Hospital, Xiushan, Chongqing, 409900, China.
  • 5. Laboratory of Stem Cells, Institute of Cell Biology, College of Life Sciences, Zhejiang University, Zhejiang, 310058, Hangzhou, China. [email protected].
  • 6. Clinical Medical College, Zhejiang Chinese Medical University, Zhejiang, 310053, Hangzhou, China. [email protected].
PMID: 31151466 DOI: 10.1186/s13287-019-1234-9
Abstract

Background: Induced 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.

Methods: Human 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.

Results: The 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.

Conclusions: These 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.

Keywords
CD200+/ITGA6+ epithelial stem cells; Hair follicle; Induced pluripotent stem cells; Skin defect.
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