Yang Ruifeng, Xu Xiaowei
Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, USA.
J Vis Exp. 2013 Apr 6(74):3194. doi: 10.3791/3194.
Hair follicles undergo lifelong growth and hair cycle is a well-controlled process involving stem cell proliferation and quiescence. Hair bulge is a well-characterized niche for adult stem cells. This segment of the outer root sheath contains a number of different types of stem cells, including epithelial stem cells, melanocyte stem cells and neural crest like stem cells. Hair follicles represent an accessible and rich source for different types of human stem cells. We and others have isolated neural crest stem cells (NCSCs) from human fetal and adult hair follicles. These human stem cells are label-retaining cells and are capable of self-renewal through asymmetric cell division in vitro. They express immature neural crest cell markers but not differentiation markers. Our expression profiling study showed that they share a similar gene expression pattern with murine skin immature neural crest cells. They exhibit clonal multipotency that can give rise to myogenic, melanocytic, and neuronal cell lineages after in vitro clonal single cell culture. Differentiated cells not only acquire lineage-specific markers but also demonstrate appropriate functions in ex vivo conditions. In addition, these NCSCs show differentiation potential toward mesenchymal lineages. Differentiated neuronal cells can persist in mouse brain and retain neuronal differentiation markers. It has been shown that hair follicle derived NCSCs can help nerve regrowth, and they improve motor function in mice transplanted with these stem cells following transecting spinal cord injury. Furthermore, peripheral nerves have been repaired with stem cell grafts, and implantation of skin-derived precursor cells adjacent to crushed sciatic nerves has resulted in remyelination. Therefore, the hair follicle/skin derived NCSCs have already shown promising results for regenerative therapy in preclinical models. Somatic cell reprogramming to induced pluripotent stem (iPS) cells has shown enormous potential for regenerative medicine. However, there are still many issues with iPS cells, particularly the long-term effect of oncogene/virus integration and potential tumorigenicity of pluripotent stem cells have not been adequately addressed. There are still many hurdles to be overcome before iPS cells can be used for regenerative medicine. Whereas the adult stem cells are known to be safe and they have been used clinically for many years, such as bone marrow transplant. Many patients have already benefited from the treatment. Autologous adult stem cells are still preferred cells for transplantation. Therefore, the readily accessible and expandable adult stem cells in human skin/hair follicles are a valuable source for regenerative medicine.
毛囊经历终身生长，毛发周期是一个受到良好控制的过程，涉及干细胞的增殖和静止。毛囊隆突是已被充分表征的成体干细胞微环境。外根鞘的这一部分包含许多不同类型的干细胞，包括上皮干细胞、黑素细胞干细胞和类神经嵴干细胞。毛囊是不同类型人类干细胞的一个易于获取且丰富的来源。我们和其他人已从人胎儿和成人毛囊中分离出神经嵴干细胞（NCSCs）。这些人类干细胞是标记保留细胞，能够在体外通过不对称细胞分裂进行自我更新。它们表达未成熟神经嵴细胞标志物，但不表达分化标志物。我们的表达谱研究表明，它们与小鼠皮肤未成熟神经嵴细胞具有相似的基因表达模式。它们表现出克隆多能性，在体外克隆单细胞培养后可产生肌源性、黑素细胞性和神经元细胞谱系。分化细胞不仅获得谱系特异性标志物，而且在体外条件下还表现出适当的功能。此外，这些神经嵴干细胞显示出向间充质谱系的分化潜力。分化的神经元细胞可以在小鼠大脑中持续存在并保留神经元分化标志物。已经表明，毛囊来源的神经嵴干细胞可以帮助神经再生，并且在脊髓横断损伤后移植这些干细胞的小鼠中，它们改善了运动功能。此外，已经用干细胞移植修复了周围神经，并且在坐骨神经挤压附近植入皮肤来源的前体细胞已导致髓鞘再生。因此，毛囊/皮肤来源的神经嵴干细胞在临床前模型的再生治疗中已经显示出有希望的结果。体细胞重编程为诱导多能干细胞（iPS细胞）在再生医学中已显示出巨大潜力。然而，iPS细胞仍然存在许多问题，特别是致癌基因/病毒整合的长期影响以及多能干细胞的潜在致瘤性尚未得到充分解决。在iPS细胞可用于再生医学之前，仍有许多障碍需要克服。而成体干细胞已知是安全的，并且它们已经在临床上使用多年，例如骨髓移植。许多患者已经从这种治疗中受益。自体成体干细胞仍然是移植的首选细胞。因此，人皮肤/毛囊中易于获取且可扩增的成体干细胞是再生医学的宝贵来源。
