Nanoscale microenvironment engineering for expanding human hair follicle stem cell and revealing their plasticity.

Nanoscale microenvironment engineering for expanding human hair follicle stem cell and revealing their plasticity.
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用于扩增人类毛囊干细胞并揭示其可塑性的纳米级微环境工程

DOI:
10.1186/s12951-021-00840-5
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发表时间:
2021-03-31
影响因子:
10.2
通讯作者:
Hu Z
Hu Z
中科院分区:
工程技术1区
文献类型:
--
作者:
Chen P;Zhang F;Fan Z;Shen T;Liu B;Chen R;Qu Q;Wang J;Miao Y;Hu Z

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研究背景周期性再生的毛囊为研究组织再生和干细胞稳态提供了一个很好的研究模型。毛囊干细胞(HFSC)的周期性激活和分化促进了毛发再生的周期性发作。HFSC代表了研究组织再生和体干细胞稳态的极好范例。然而,这些重要的研究受到阻碍,缺乏一个培养系统,能够稳定地扩大人类HFSCs和调节他们的fate.ResultsHere,我们使用逐层(LBL)自组装明胶/藻酸盐构建一个纳米级的仿生细胞外基质(ECM)的HFSC人口。LbL涂层为单个细胞提供ECM和机械支持,有助于在一定程度上维持CD 200 +α6+HFSC群体。添加关键信号分子(FGF-7和VEGF-A)模拟干细胞微环境的最低必需组分,从而有效且稳定地扩增HFSC并维持CD 200 +α6+HFSC群体。结论该系统能有效地减少HFSCs的微环境,稳定扩增HFSCs,并揭示其可塑性。因此,我们的研究提供了一个新的工具,毛囊重建和干细胞稳态的研究。
BackgroundPeriodically regenerated hair follicles provide an excellent research model for studying tissue regeneration and stem cell homeostasis. Periodic activation and differentiation of hair follicle stem cells (HFSCs) fuel cyclical bouts of hair regeneration. HFSCs represent an excellent paradigm for studying tissue regeneration and somatic stem cell homeostasis. However, these crucial studies are hampered by the lack of a culture system able to stably expand human HFSCs and regulate their fate.ResultsHere, we use layer-by-layer (LbL) self-assembly with gelatin/alginate to construct a nanoscale biomimetic extracellular matrix (ECM) for an HFSC population. The LbL coating provides ECM and mechanical support for individual cells, which helps to maintain the CD200+α6+HFSC population to a certain extent. Addition of key signal molecules (FGF-7 and VEGF-A) simulates the minimum essential components of the stem cell microenvironment, thereby effectively and stably expanding HFSCs and maintaining the CD200+α6+HFSC population. Subsequently, BMP2 loaded to the nanocoated layer, as a slow-release signal molecule, activates BMP signaling to regulate HFSCs’ fate in order to obtain a purified CD200+α6+HFSC population.ConclusionThis system can minimize the microenvironment of HFSCs; thus, stably amplifying HFSCs and revealing their plasticity. Our study thus provides a new tool for studies of hair follicle reconstruction and stem cell homeostasis.
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