毛囊是表皮细胞连续形成的袋样上皮，通过上皮细胞不断分裂、增殖，为毛发生长提供养分，支持毛发的生长和更新。近日，研究人员首次利用体外培养的人干细胞生成皮肤类器官，然后成功移植到裸鼠身上并顺利长出人类皮肤和毛囊。相关研究结果发表在Nature杂志上。
该研究建立了干细胞3D培养技术，将人源干细胞在皮肤样器官的球状细胞群中培养了大约150天。细胞团的内部代表皮肤的顶层，即表皮，细胞团的外部代表皮肤的底层，即真皮，获得的皮肤器官类似于胎儿面部皮肤和毛发。研究人员还开发出一种新的配方，能够使皮肤类器官在培养约70天后产生毛囊。毛囊生长时，根呈放射状向外延伸。在皮肤类器官孵化期结束后，研究人员测试了皮肤是否能与裸鼠皮肤结合。结果显示，移植到裸鼠身上的皮肤类器官有一半以上长出了人的毛囊。
该研究表明有机合成的毛状皮肤可与小鼠皮肤结合，为皮肤重建手术提供了潜在软组织和毛囊来源，也将对皮肤疾病建模和治疗提供重要工具。
推荐阅读原文：
Hair-bearing human skin generated entirely from pluripotent stem cells.
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 pain. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met. 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.
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