皮肤附属器官再生微环境的研究

Loss of skin appendages in severe skin injury, such as hair follicles and other structures could not be reformed. Lack of skin appendages, not only affect the appearance of the skin, but also affects the practical functions of the skin. New research showed that the excisional skin lesions in adult mice still exert the potential to regenerate hair follicles. Our early findings show that theLy6C+CX3CR1-macrophage subsets in skin damage activate hair follicle stem cells have a decisive role, further study found that macrophages through the release of TNF-α to activate LGR5+ hair follicle stem cells, so that follicles enter the growth cycle and regeneration. The objective of this study is to further explore these factors that activate LGR5+ hair follicle stem cells. We have established an efficient LGR5+ hair follicle stem cells isolated and cultured procedures, and hair follicles restructuring experimental techniques, and combined with the cDNA microarray to identify candidates released by Ly6C+ macrophages, which promotes LGR5+ hair follicle stem cells regenerate via hair follicles micro-environmental. Because no hair follicle regeneration after skin injury, as well as ordinary male hair loss are caused by the lack of hair follicle stem cells regeneration microenvironment, so the study have important theoretical and practical value to these problems.

皮肤严重损伤后，损失的皮肤附属器官如毛囊等结构不能够重新形成。皮肤附属器官的缺失，不但影响皮肤的外观，还影响皮肤的诸多功能。最新研究表明成年小鼠的皮肤切除损伤中仍然具备毛囊再生的能力。申请人的前期研究结果表明皮肤损伤后Ly6C+CX3CR1-巨噬细胞亚群对毛囊干细胞的激活有着决定性作用，进一步的研究发现该巨噬细胞是通过释放TNF-α来激活LGR5+毛囊干细胞，从而使毛囊进入生长周期和再生的。本研究的目标是进一步发现能激活LGR5+毛囊干细胞的活性物质。申请人已经建立了完整的LGR5+毛囊干细胞分离培养、毛囊重组等实验技术和方案，并与基因芯片筛选到的Ly6C+巨噬细胞释放的候选活性因子相结合，进一步的确定能促进LGR5+毛囊干细胞再生毛囊微环境因子。由于皮肤损伤后无毛囊再生，以及普通的男性脱发都是毛囊干细胞缺少再生的微环境造成的，所以该研究对这些问题的解决都有重要的理论和实际应用价值。

皮肤严重损伤后，损失的皮肤附属器官如毛囊等结构不能够重新形成。皮肤附属器官的缺失，不但影响皮肤的外观，还影响皮肤的诸多功能。最新研究表明成年小鼠的皮肤切除损伤中仍然具备毛囊再生的能力。申请人的前期研究结果表明皮肤损伤后Ly6C+CX3CR1-巨噬细胞亚群对毛囊干细胞的激活有着决定性作用，进一步的研究发现该巨噬细胞是通过释放TNF-α来激活LGR5+毛囊干细胞，从而使毛囊进入生长周期和再生的。本研究的目标是进一步发现能激活LGR5+毛囊干细胞的活性物质。申请人已经建立了完整的LGR5+毛囊干细胞分离培养、毛囊重组等实验技术和方案，并与基因芯片筛选到的Ly6C+巨噬细胞释放的候选活性因子相结合，进一步的确定能促进LGR5+毛囊干细胞再生毛囊微环境因子。由于皮肤损伤后无毛囊再生，以及普通的男性脱发都是毛囊干细胞缺少再生的微环境造成的，所以该研究对这些问题的解决都有重要的理论和实际应用价值。本研究利用近20余种转基因小鼠证明了巨噬细胞-TNF-a在损伤诱导的毛囊再生中的核心作用。相关研究成果发表在Nature Communications (Wang, Chen et al. 2017)中，该论文为国内毛囊再生研究领域中首篇Nature系列文章。