小柯机器人

科学家首次培育出能够生长毛发的人类皮肤
2020-06-04 16:29

美国哈佛医学院Karl R. Koehler研究组在研究中取得突破性进展。他们的最新工作表明,利用多能干细胞能够培育出生长毛发的人类皮肤。这一研究成果于2020年6月3日在线发表于《自然》。

研究人员报道了类器官体培养系统,该系统从人的多能干细胞中产生复杂的皮肤。研究人员使用转化生长因子β(TGFβ)和成纤维细胞生长因子(FGF)信号途径的逐步调节,从而在球形细胞聚集体中诱导出颅上皮细胞和神经嵴细胞。在4到5个月的培养中,研究人员观察到类似囊肿的皮肤类器官体出现,该类器官体由分层的表皮、富含脂肪的真皮以及有皮脂腺的色素性毛囊组成。
 
感觉神经元和雪旺氏细胞网络形成神经样束,以类器官体毛囊中的默克尔细胞为靶标,模仿与人类触摸相关的神经回路。单细胞RNA测序和与胎儿标本的直接比较表明,在发育的中期,皮肤类器官体与人类胎儿的面部皮肤相同。此外,研究人员表明,皮肤类器官体被移植到裸鼠上时会形成平坦的有毛皮肤。
 
总之,这些结果表明,几乎完整的皮肤可以在体外自我组装,并可以在体内重建皮肤。研究人员预计这一皮肤类器官体将为人类皮肤发育、疾病建模和重建手术奠定基础。
 
据了解,皮肤是多层器官,并带有附属器官(即毛囊和腺体),对于调节体温和体液滞留,防止外界压力以及介导触觉和疼痛感至关重要。在体外培养和生物工程移植物中重建完整皮肤是一项艰难的生物医学挑战。
 
附:英文原文

Title: Hair-bearing human skin generated entirely from pluripotent stem cells

Author: Jiyoon Lee, Cyrus C. Rabbani, Hongyu Gao, Matthew R. Steinhart, Benjamin M. Woodruff, Zachary E. Pflum, Alexander Kim, Stefan Heller, Yunlong Liu, Taha Z. Shipchandler, Karl R. Koehler

Issue&Volume: 2020-06-03

Abstract: The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain1,2. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met3,4,5,6,7,8,9. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4–5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery.

DOI: 10.1038/s41586-020-2352-3

Source: https://www.nature.com/articles/s41586-020-2352-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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