Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro
Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro
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DOI：
10.1038/s41536-019-0086-3
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发表时间：
2020-01-06
影响因子：
7.2
通讯作者：
Chang, William G.
中科院分区：
文献类型：
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作者：
Kosyakova, Natalia;Kao, Derek D.;Chang, William G.
可灌注微血管网（mu VN）的形成对于实体器官的组织工程是至关重要的。基质细胞可以支持内皮细胞（EC）自组装成一个μ VN，但不同的基质细胞群体可能在这个过程中发挥不同的作用。在这里，我们描述了两个广泛使用的基质细胞群，成纤维细胞（FB）和周细胞（PC），对μ VN形成的差异效应。我们研究了添加定义的基质细胞群对来自人内皮集落形成细胞（ECFC）的EC自组装成在微流体室内浇铸的纤维蛋白凝胶中可灌注的μ VN的影响。单独的EC不能完全组装可灌注的mu VN。人肺FB刺激微流体装置内EC内衬的μ VN的形成。RNA-seq分析表明，FB产生高水平的肝细胞生长因子（HGF）。添加重组HGF可改善，而c-MET抑制剂Capmatinib（INCB 28060）可减少装置内的mu VN形成。人胎盘PC不能替代FB，但在FB存在下，PC与EC紧密结合，形成共同的基底膜，在细胞间延伸微丝，并减小微血管直径。不同类型的基质细胞在内皮细胞组装微血管中发挥不同的功能。FB通过提供旁分泌生长因子支持μ VN形成，而PC直接与EC相互作用以改变微血管形态。
Formation of a perfusable microvascular network (mu VN) is critical for tissue engineering of solid organs. Stromal cells can support endothelial cell (EC) self-assembly into a mu VN, but distinct stromal cell populations may play different roles in this process. Here we describe the differential effects that two widely used stromal cell populations, fibroblasts (FBs) and pericytes (PCs), have on mu VN formation. We examined the effects of adding defined stromal cell populations on the self-assembly of ECs derived from human endothelial colony forming cells (ECFCs) into perfusable mu VNs in fibrin gels cast within a microfluidic chamber. ECs alone failed to fully assemble a perfusable mu VN. Human lung FBs stimulated the formation of EC-lined mu VNs within microfluidic devices. RNA-seq analysis suggested that FBs produce high levels of hepatocyte growth factor (HGF). Addition of recombinant HGF improved while the c-MET inhibitor, Capmatinib (INCB28060), reduced mu VN formation within devices. Human placental PCs could not substitute for FBs, but in the presence of FBs, PCs closely associated with ECs, formed a common basement membrane, extended microfilaments intercellularly, and reduced microvessel diameters. Different stromal cell types provide different functions in microvessel assembly by ECs. FBs support mu VN formation by providing paracrine growth factors whereas PCs directly interact with ECs to modify microvascular morphology.