Wu Wei, Wu Xiao-Li, Ji Yu-Qing, Gao Zhen
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
Department of Plastic and Reconstructive Surgery, Shanghai General Hospital, Shanghai 200080, P.R. China.
Mol Med Rep. 2017 Jul;16(1):95-100. doi: 10.3892/mmr.2017.6585. Epub 2017 May 16.
A specialized quiescent population of hair follicle stem cells, residing in the hair follicle outer root sheath cells (ORSCs), has previously demonstrated pluripotency for differentiation into neural stem cells (NSCs). A previous study indicated that nestin‑positive hair follicle ORSCs are able to differentiate into neurons. However, little has been reported on the isolation of nestin‑negative human ORSCs and whether they can successfully differentiate into neurons in vitro. In the present study, nestin‑positive ORSCs were significantly reduced with a prolonged incubation time in vitro. Following 9 days of primary culture, nestin‑expressing ORSCs disappeared entirely, and ORSCs remained nestin‑negative following 5 days of subculture. Notably, nestin was identified in ORSCs following a three‑step process of neuro‑induction. In addition, neruodevelopmental markers were detected in the ORSC‑derived nestin‑positive spherical cell mass, including the induction of the neuronal specific markers growth associated protein‑43, neurotensin receptor‑3 and p75 neurotrophin receptor, and also the gliocyte markers, glial fibrillary acidic protein and S100. These sphere‑forming cells did not express the mature neuron‑associated markers neurofilament medium, neuronal nuclei and neuron‑specific enolase, which suggested that sphere‑forming cells may preferentially differentiate into neural stem cell‑like cells as opposed to mature neurons or neurogliocyte. In conclusion, ORSC‑driven neural differentiation may be a suitable treatment strategy for neurodegenerative diseases and may possess an important value in regenerative medicine.
存在于毛囊外根鞘细胞（ORSCs）中的一类特殊的静止毛囊干细胞群，先前已证明其具有分化为神经干细胞（NSCs）的多能性。先前的一项研究表明，巢蛋白阳性的毛囊ORSCs能够分化为神经元。然而，关于巢蛋白阴性的人ORSCs的分离以及它们是否能在体外成功分化为神经元的报道较少。在本研究中，随着体外培养时间的延长，巢蛋白阳性的ORSCs显著减少。原代培养9天后，表达巢蛋白的ORSCs完全消失，传代培养5天后，ORSCs仍为巢蛋白阴性。值得注意的是，经过三步神经诱导过程后，在ORSCs中检测到了巢蛋白。此外，在源自ORSCs的巢蛋白阳性球形细胞团中检测到了神经发育标志物，包括神经元特异性标志物生长相关蛋白43、神经降压素受体3和p75神经营养因子受体的诱导表达，以及胶质细胞标志物胶质纤维酸性蛋白和S100。这些形成球体的细胞不表达成熟神经元相关标志物神经丝中型蛋白、神经元细胞核和神经元特异性烯醇化酶，这表明形成球体的细胞可能优先分化为神经干细胞样细胞，而不是成熟神经元或神经胶质细胞。总之，ORSC驱动的神经分化可能是治疗神经退行性疾病的一种合适策略，在再生医学中可能具有重要价值。
