Preparation of hair beads and hair follicle germs for regenerative medicine
Preparation of hair beads and hair follicle germs for regenerative medicine
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DOI：
10.1016/j.biomaterials.2019.05.003
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发表时间：
2019-08-01
期刊：
影响因子：
14
通讯作者：
Fukuda, Junji
中科院分区：
文献类型：
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作者：
Kageyama, Tatsuto;Yan, Lei;Fukuda, Junji
毛发再生医学是一种很有前途的治疗脱发的方法，在此过程中，自体毛囊干细胞被移植到脱发区域以再生毛发。由于作为单细胞悬浮液移植的细胞几乎不产生毛发，因此已经探索了移植前的三维（3D）组织工程以改善这一过程。在这里，我们提出了一种通过细胞包裹的胶原滴的自发收缩来制造富含胶原蛋白的细胞聚集体（称为发珠（HB））的方法。将小鼠胚胎间充质细胞或人毛乳头细胞包封在2 μ l胶原微凝胶中，其在3天的培养期间体积浓缩> 10倍。有趣的是，HB收缩归因于肌球蛋白II驱动的吸引力，并涉及卵泡基因的上调。在3天的培养期间，接种在U形微孔中的具有上皮细胞的单个HB形成哑铃状结构，其包含各自的聚集体（称为基于珠粒的毛囊胚芽，bbHFG）。bbHFG在皮内移植到裸鼠背部后有效地产生毛囊。使用自动点样器，这种方法可扩展以制备大量bbHFG，这对于临床应用很重要。因此，这可能代表了一种稳健和实用的方法，用于制备用于毛发再生医学的胚样组织。
Hair regenerative medicine is a promising approach for hair loss, during which autologous follicular stem cells are transplanted into regions of hair loss to regenerate hairs. Because cells transplanted as a single cell suspension scarcely generate hairs, the engineering of three-dimensional (3D) tissues before transplantation has been explored to improve this process. Here, we propose an approach to fabricate collagen-enriched cell aggregates, named hair beads (HBs), through the spontaneous constriction of cell-encapsulated collagen drops. Mouse embryonic mesenchymal cells or human dermal papilla cells were encapsulated in 2-mu l collagen microgels, which were concentrated > 10-fold in volume during 3 days of culture. Interestingly, HB constriction was attributed to attraction forces driven by myosin II and involved the upregulation of follicular genes. Single HBs with epithelial cells seeded in U-shaped microwells formed dumbbell-like structures comprising respective aggregates (named bead-based hair follicle germs, bbHFGs), during 3 days of culture. bbHFGs efficiently generated hair follicles upon intracutaneous transplantation into the backs of nude mice. Using an automated spotter, this approach was scalable to prepare a large number of bbHFGs, which is important for clinical applications. Therefore, this could represent a robust and practical approach for the preparation of germ-like tissues for hair regenerative medicine.