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Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro.

ABSTRACT: Formation of a perfusable microvascular network (?VN) is critical for tissue engineering of solid organs. Stromal cells can support endothelial cell (EC) self-assembly into a ?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 ?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 ?VNs in fibrin gels cast within a microfluidic chamber. ECs alone failed to fully assemble a perfusable ?VN. Human lung FBs stimulated the formation of EC-lined ?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 ?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 ?VN formation by providing paracrine growth factors whereas PCs directly interact with ECs to modify microvascular morphology.

SUBMITTER: Kosyakova N

PROVIDER: S-EPMC6944695 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro.

Kosyakova Natalia N Kao Derek D DD Figetakis Maria M López-Giráldez Francesc F Spindler Susann S Graham Morven M James Kevin J KJ Won Shin Jee J Liu Xinran X Tietjen Gregory T GT Pober Jordan S JS Chang William G WG

NPJ Regenerative medicine 20200106

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 o ...[more]

PMID: 31934351

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Project description:Pericytes are unique, multi-functional mural cells localized at the abluminal side of the perivascular space in microvessels. Originally discovered in 19th century, pericytes had drawn less attention until decades ago mainly due to lack of specific markers. Recently, however, a growing body of evidence has revealed that pericytes play various important roles: development and maintenance of blood-brain barrier (BBB), regulation of the neurovascular system (e.g., vascular stability, vessel formation, cerebral blood flow, etc.), trafficking of inflammatory cells, clearance of toxic waste products from the brain, and acquisition of stem cell-like properties. In the neurovascular unit, pericytes perform these functions through coordinated crosstalk with neighboring cells including endothelial, glial, and neuronal cells. Dysfunction of pericytes contribute to a wide variety of diseases that lead to cognitive impairments such as cerebral small vessel disease (SVD), acute stroke, Alzheimer's disease (AD), and other neurological disorders. For instance, in SVDs, pericyte degeneration leads to microvessel instability and demyelination while in stroke, pericyte constriction after ischemia causes a no-reflow phenomenon in brain capillaries. In AD, which shares some common risk factors with vascular dementia, reduction in pericyte coverage and subsequent microvascular impairments are observed in association with white matter attenuation and contribute to impaired cognition. Pericyte loss causes BBB-breakdown, which stagnates amyloid ? clearance and the leakage of neurotoxic molecules into the brain parenchyma. In this review, we first summarize the characteristics of brain microvessel pericytes, and their roles in the central nervous system. Then, we focus on how dysfunctional pericytes contribute to the pathogenesis of vascular cognitive impairment including cerebral 'small vessel' and 'large vessel' diseases, as well as AD. Finally, we discuss therapeutic implications for these disorders by targeting pericytes.

Dataset Information

Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro.

Publications

Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro.

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