Repair of large skin defects caused by burns, trauma, or tumor operations is a clinical challenge. Hair follicle stem cells (HFSCs) are involved in epithelialization of wounds, formation of new hair follicles and promote vascularization in the newly formed skin, and human acellular amniotic membrane (hAAM) is a promising scaffold for skin substitute. Here, we investigated the ability of rat HFSCs (rHFSCs) combined with an hAAM to repair full thickness skin defects in nude mice. The effect of the rHFSC‐hAAM composite on the repair of skin defects in nude mice was assessed by hematoxylin and eosin staining, immunohistochemistry, and EdU‐labeled cell tracking. Isolated and cultured rHFSCs had strong cloning and proliferation potentials. Immunofluorescence staining and flow cytometry assays showed that rHFSCs expressed high levels of integrin α6, CK15, p63, and Sox9. Cells cultured in hAAM showed flaky and cluster‐like morphology and were able to adhere and grow effectively. After transplantation, the rHFSC‐hAAM composite promoted wound healing in nude mice. Moreover, cells in the rHFSC‐hAAM composite were directly involved in hair follicle formation and angiogenesis of tissue around the hair follicle. These results provide an experimental and theoretical basis for the clinical application of HFSCs in repair of human skin defects and a new approach for skin tissue engineering.

中文翻译：

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毛囊干细胞结合人类同种异体脱细胞羊膜修复裸鼠的全层皮肤缺损。

修复由烧伤，外伤或肿瘤手术引起的大皮肤缺陷是一项临床挑战。毛囊干细胞（HFSC）参与伤口的上皮形成，新毛囊的形成并促进新形成的皮肤中的血管形成，而人类脱细胞羊膜（hAAM）是一种有希望替代皮肤的支架。在这里，我们调查了与hAAM结合的大鼠HFSC（rHFSC）修复裸鼠全层皮肤缺损的能力。通过苏木精和曙红染色，免疫组织化学和EdU标记的细胞追踪评估了rHFSC-hAAM复合材料对裸鼠皮肤缺损修复的作用。分离和培养的rHFSCs具有很强的克隆和增殖潜力。免疫荧光染色和流式细胞仪分析表明，rHFSCs表达高水平的整合素α6，CK15，p63和Sox9。在hAAM中培养的细胞表现出片状和簇状形态，能够有效粘附并生长。移植后，rHFSC-hAAM复合材料促进了裸鼠的伤口愈合。此外，rHFSC-hAAM复合材料中的细胞直接参与毛囊的形成和毛囊周围组织的血管生成。这些结果为HFSCs在人类皮肤缺损的修复中的临床应用和皮肤组织工程的新方法提供了实验和理论基础。rHFSC-hAAM复合材料中的细胞直接参与毛囊的形成和毛囊周围组织的血管生成。这些结果为HFSCs在人类皮肤缺损的修复中的临床应用和皮肤组织工程的新方法提供了实验和理论基础。rHFSC-hAAM复合材料中的细胞直接参与毛囊的形成和毛囊周围组织的血管生成。这些结果为HFSCs在人类皮肤缺损的修复中的临床应用和皮肤组织工程的新方法提供了实验和理论基础。