Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro
| Autor: | Francesc López-Giráldez, Maria Figetakis, Jee Won Shin, Xinran Liu, Gregory T. Tietjen, Derek D. Kao, Kevin J. James, Natalia Kosyakova, William G. Chang, Morven Graham, Jordan S. Pober, Susann Spindler |
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| Rok vydání: | 2020 |
| Předmět: |
Stromal cell
Biomedical Engineering lcsh:Medicine Medicine (miscellaneous) Article 03 medical and health sciences Paracrine signalling 0302 clinical medicine Tissue engineering medicine Cell adhesion Microvessel 030304 developmental biology Basement membrane 0303 health sciences Chemistry lcsh:R Cell Biology Cell biology Endothelial stem cell medicine.anatomical_structure Regenerative medicine Hepatocyte growth factor Gene expression 030217 neurology & neurosurgery Developmental Biology medicine.drug |
| Zdroj: | NPJ Regenerative Medicine npj Regenerative Medicine, Vol 5, Iss 1, Pp 1-12 (2020) |
| ISSN: | 2057-3995 |
| Popis: | 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 describe the differential effects that two widely used stromal cell populations, fibroblasts (FBs) and pericytes (PCs), have on μVN 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 μVNs in fibrin gels cast within a microfluidic chamber. ECs alone failed to fully assemble a perfusable μVN. Human lung FBs stimulated the formation of EC-lined μVNs 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 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, extended microfilaments intercellularly, and reduced microvessel diameters. 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. |
| Databáze: | OpenAIRE |
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