Nakajima Rikuma, Tate Yoshiki, Yan Lei, Kageyama Tatsuto, Fukuda Junji
Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa 240-8501, Japan.
Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa 240-8501, Japan; Kanagawa Institute of Industrial Science and Technology, 3-2-1 Sakado Takatsu-ku, Kawasaki, Kanagawa 213-0012, Japan; Japan Science and Technology Agency (JST)-PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
J Biosci Bioeng. 2021 Jun;131(6):679-685. doi: 10.1016/j.jbiosc.2021.02.001. Epub 2021 Mar 5.
Hair regenerative medicine has emerged as a promising treatment strategy for severe hair loss, such as end-stage androgenetic alopecia. Various approaches to engineering three-dimensional tissue grafts have been explored since they drive the ability to regenerate hair follicles when transplanted. In the present study, we demonstrated the assembly of human adipose-derived stem cells (hASCs) into hair follicle germ (HFG)-like aggregates for de novo hair regeneration. We mixed human dermal papilla cells (hDPCs), murine embryonic epithelial cells, and hASCs in suspension, and allowed them to form aggregates. During three days of culture, cells initially formed a single aggregate with a random distribution of the three cell types, but the epithelial and dermal papilla cells subsequently separated from each other and formed a dumbbell-shaped HFG, with hASCs localized on the hDPC aggregate side. The involvement of hASCs significantly increased gene expression associated with hair morphogenesis compared to HFGs without hASCs. The self-organization of the three cell types was observed in our scalable lab-made chip device. HFGs containing hASCs efficiently generated hair shafts upon transplantation to nude mice, while only a few shafts were generated with HFGs without hASCs. This approach may be a promising strategy for fabricating tissue grafts for hair regenerative medicine.
毛发再生医学已成为一种治疗严重脱发（如终末期雄激素性脱发）的有前景的治疗策略。自从发现三维组织移植物在移植后具有驱动毛囊再生的能力以来，人们探索了各种构建三维组织移植物的方法。在本研究中，我们展示了将人脂肪来源干细胞（hASC）组装成毛囊胚（HFG）样聚集体用于从头毛发再生。我们将人真皮乳头细胞（hDPC）、小鼠胚胎上皮细胞和hASC悬浮混合，使其形成聚集体。在三天的培养过程中，细胞最初形成一个单一聚集体，三种细胞类型随机分布，但上皮细胞和真皮乳头细胞随后彼此分离，形成一个哑铃形的HFG，hASC定位于hDPC聚集体一侧。与不含hASC的HFG相比，hASC的参与显著增加了与毛发形态发生相关的基因表达。在我们可扩展的实验室自制芯片装置中观察到了三种细胞类型的自组织。含有hASC的HFG移植到裸鼠后能有效产生毛干，而不含hASC的HFG仅产生少数毛干。这种方法可能是一种用于毛发再生医学组织移植物制造的有前景的策略。
