GSE122389
Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro
Aims: Formation of a perfusable microvascular network (µVN) is critical for tissue engineering of solid organs. Stromal cells can support endothelial cell (EC) self-assembly into a µVN, but distinct stromal cell populations may play different roles in this process. Here we investigated the effects that two widely used stromal cells populations, fibroblasts (FBs) and pericytes (PCs), have on µVN formation.     Methods and results: We examined the effects of adding defined stromal cell populations on the self-assembly of ECs derived from human endothelial colony forming cells (HECFCs) into perfusable µVNs in fibrin gels cast within a microfluidics chamber. ECs alone fail to fully assemble a perfusable µVN. Human lung FBs stimulate the formation of EC lined µVNs within microfluidic devices. RNA-seq analysis suggested that FBs produce high levels of hepatocyte growth factor (HGF), and addition of recombinant HGF improved µVN 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, extend microfilaments intercellularly, and reduced microvessel diameters.   Conclusions: Different stromal cell types provide different functions in microvessel assembly by ECs. FBs support µVN formation by providing paracrine growth factors whereas PCs directly interact with ECs to modify microvascular morphology. Overall design: Examination of gene expression in pericyte and fibroblast cells.