Collagen scaffold microenvironments modulate cell lineage commitment for differentiation of bone marrow cells into regulatory dendritic cells.
Collagen scaffold microenvironments modulate cell lineage commitment for differentiation of bone marrow cells into regulatory dendritic cells.
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胶原支架微环境调节细胞谱系定向，使骨髓细胞分化为调节性树突状细胞
DOI：
10.1038/srep42049
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发表时间：
2017-02-07
影响因子：
4.6
通讯作者：
Jing Z
中科院分区：
文献类型：
--
作者：
Fang Y;Wang B;Zhao Y;Xiao Z;Li J;Cui Y;Han S;Wei J;Chen B;Han J;Meng Q;Hou X;Luo J;Dai J;Jing Z
微环境对细胞的生存和功能调节起着关键作用，并指导细胞命运的决定。迄今为止，DC的生物学功能已被广泛研究。然而，微环境对骨髓细胞（BMCs）分化为树突状细胞（DCs）的影响还没有很好的定义。在这里，我们建立了一个3D胶原支架微环境，以研究这种3D胶原支架是否可以为BMCs分化为专门的DC提供一个有利的生态位。我们发现，嵌入在三维胶原支架中的BMCs分化成DC的一个独特的子集，与在二维培养中生长的那些相比，表现出高表达CD11b和低表达CD11c，共刺激分子（CD40，CD80，CD83和CD86）和MHC-II分子。体外培养的DC具有较弱的抗原摄取能力和抑制T细胞增殖的能力，体内移植后具有较强的免疫调节功能，可减轻同种异体迟发型超敏反应。因此，在3D胶原支架中分化的DC被定义为调节性DC，表明胶原支架微环境可能在调节DC的谱系定型中起重要作用，因此可能被用作产生特化DC的有前途的工具。
The microenvironment plays a pivotal role for cell survival and functional regulation, and directs the cell fate determination. The biological functions of DCs have been extensively investigated to date. However, the influences of the microenvironment on the differentiation of bone marrow cells (BMCs) into dendritic cells (DCs) are not well defined. Here, we established a 3D collagen scaffold microenvironment to investigate whether such 3D collagen scaffolds could provide a favourable niche for BMCs to differentiate into specialised DCs. We found that BMCs embedded in the 3D collagen scaffold differentiated into a distinct subset of DC, exhibiting high expression of CD11b and low expression of CD11c, co-stimulator (CD40, CD80, CD83, and CD86) and MHC-II molecules compared to those grown in 2D culture. DCs cultured in the 3D collagen scaffold possessed weak antigen uptake ability and inhibited T-cell proliferation in vitro; in addition, they exhibited potent immunoregulatory function to alleviate allo-delay type hypersensitivity when transferred in vivo. Thus, DCs differentiated in the 3D collagen scaffold were defined as regulatory DCs, indicating that collagen scaffold microenvironments probably play an important role in modulating the lineage commitment of DCs and therefore might be applied as a promising tool for generation of specialised DCs.