Microenvironmental Reprogramming of Human Dermal Papilla Cells for Hair Follicle Tissue Engineering.
Microenvironmental Reprogramming of Human Dermal Papilla Cells for Hair Follicle Tissue Engineering.
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DOI：
10.1016/j.actbio.2022.11.004
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发表时间：
2022-11
影响因子：
9.7
通讯作者：
Zhen Liu;Junfei Huang;Deni Kang;Yi Zhou;L. Du;Qian Qu;Jin Wang;Lihong Wen;Danlan Fu
中科院分区：
文献类型：
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作者：
Zhen Liu;Junfei Huang;Deni Kang;Yi Zhou;L. Du;Qian Qu;Jin Wang;Lihong Wen;Danlan Fu
人毛乳头细胞(HDPC)毛发诱导潜能的恢复是毛发再生的一个巨大挑战。到目前为止，许多研究表明，三维(3-D)培养在毛囊(HF)新生方面显示出更好的疗效。然而，成熟的HF不能在不完整的微环境中再生。本研究开发了一种优化的三维共培养系统，通过模拟生存微环境来恢复hDPC的毛发诱导特性。结果，Matrigel包裹的hDPC自发形成hDPC聚集体(HDPA)，与超低贴壁培养相比，hDPC聚集体显示出更好的活性、更高的增殖率、更少的凋亡和缺氧。有趣的是，与毛发基质细胞和真皮鞘杯细胞共培养，与条件培养液相比，hDPA毛发再生相关基因的表达进一步增强，并改善了成熟HF的诱导。此外，这些具有较高毛发诱导性的hDPA可以大规模生产，并易于分离用于基因表达检测。最后，mRNA测序、PCR和WB结果表明，共培养的仿生微环境刺激了规范的Wnt信号通路，抑制了BMP信号通路。因此，这种共培养系统将提供一个可靠的平台，允许高通量培养、测试和收获hDPA用于HF组织工程。毛囊(HF)组织工程似乎是一条出路。然而，缺乏生存的微环境无法再生成熟的头发。本研究系统地描述了一种仿生共培养方法，该方法可以产生更高质量的人毛乳头细胞聚集体(HDPA)，并且具有更好的诱导毛发性能，可以进一步用于HF组织工程。通过在Matrigel中可控地形成自组装的有机体，并与毛发基质细胞和真皮鞘杯细胞进行三次培养，hDPC的微环境被重新编程。这项工作表明，在理论上，hDPA的生产可以很容易地规模化，用于大规模的分析、分析或治疗应用。
The restoration of hair-inductive potential in human dermal papilla cells (hDPCs) is a tremendous challenge for hair regeneration. Much of the research thus far has indicated that three-dimensional (3-D) culture shows improved efficacy in hair follicle (HF) neogenesis. However, mature HF cannot regenerate in an incomplete microenvironment. This study developed an optimized 3-D co-culture system to restore the hair-inductive characteristics of hDPCs by mimicking thein-vivomicroenvironment. As a result, Matrigel-encapsulated hDPCs spontaneously formed into hDPC aggregates (hDPAs), which exhibited better activity, higher proliferation rates, and less apoptosis and hypoxia than the ultra-low attachment culture. Interestingly, the co-culture with the hair matrix cells and dermal sheath cup cells further enhanced the expression of hair regeneration-related genes of hDPAs compared to conditioned medium and improved mature HF induction. In addition, these hDPAs with higher hair inductivity could be produced on a large scale and easily separated for gene expression detection. Finally, the mRNA sequencing, PCR, and WB results showed that the co-culture biomimetic microenvironment stimulated the canonical Wnt signaling pathway and inhibited the BMP signaling pathway. Thus, this co-culture system will provide a reliable platform that allows high-throughput culture, testing, and harvesting of hDPAs for HF tissue engineering.Statement of significanceExtensive hair loss continues to be difficult to treat and causes significant patient morbidity. Hair follicle (HF) tissue engineering may seem to be a way out. However, the absence of thein-vivomicroenvironment fails to regenerate mature hairs. This study systematically described a biomimetic co-culture approach to generate better quality human dermal papilla cell aggregates (hDPAs) with improved hair inductive properties, which can be further used for HF tissue engineering. The hDPC microenvironment was reprogrammed through the controllable formation of self-assembled organoids in Matrigel and the tri-culture with hair matrix cells and dermal sheath cup cells. This work indicates that the production of hDPAs could be readily scaled, in theory for large-scale assays, analyses, or therapeutic applications.