Establishment and characterization of an embryonic pericyte cell line

Zhao, Huaning; Darden, Jordan; Chappell, John C.

doi:10.1111/micc.12461

Cited by 13 publications

(22 citation statements)

References 65 publications

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“…Another group has recently described how NG2 + -PCs could be isolated from mice genetically modified to mark PC populations with a fluorescent protein (DsRed) used to sort cells from dissociated embryonic tissue. 37 Part of the validation of these cells as PCs was the ex vivo incorporation into the blood vessels of explanted embryonic mouse skin. While this approach is quite convincing, we would argue that a simpler test of PC identity in vitro is to incorporate the cells into the microfluidic model system that we describe here.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…Pericytes seem to emerge at approximately the same time as, or even prior to, endothelial cell differentiation, homing to endothelium engaged in both vasculogenic (Payne, L.B. and Chappell, J.C., Unpublished observations) and angiogenic processes . Nevertheless, whether pericytes, or their precursors, directly engage with the developing endothelium to actively coordinate the formation of primitive blood vessels remains an ongoing area of investigation.…”

Section: Pericyte Origins and Identificationmentioning

confidence: 99%

“…71 Previous studies have suggested that the endothelium acquires pericyte associations primarily, if not exclusively, after endothelial sprouting events begin to establish basic vascular networks, perhaps allowing greater plasticity in endothelial remodeling. 66,[72][73][74] We, and others, [75][76][77][78] have found that mouse embryonic stem cells give rise not only to primitive endothelial cell networks, but also to presumptive pericytes (or pericyte precursors) during the earliest stages of cardiovascular development. 64 Pericytes seem to emerge at approximately the same time as, or even prior to, endothelial cell differentiation, homing to endothelium engaged in both vasculogenic (Payne, L.B.…”

Section: Peric Y Te Ori G In S and Identifi C Ati Onmentioning

confidence: 99%

“…and Chappell, J.C., Unpublished observations) and angiogenic processes. 64,[75][76][77][78] Nevertheless, whether pericytes, or their precursors, directly engage with the developing endothelium to actively coordinate the formation of primitive blood vessels remains an ongoing area of investigation. Insight from these studies could shed light on the involvement of pericytes in pathological conditions associated with vessel dysmorphogenesis and mis-patterning such as arteriovenous malformations and cerebral cavernous malformations.…”

Section: Peric Y Te Ori G In S and Identifi C Ati Onmentioning

confidence: 99%

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The pericyte microenvironment during vascular development

et al. 2019

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Vascular pericytes provide critical contributions to the formation and integrity of the blood vessel wall within the microcirculation. Pericytes maintain vascular stability and homeostasis by promoting endothelial cell junctions and depositing extracellular matrix (ECM) components within the vascular basement membrane, among other vital functions. As their importance in sustaining microvessel health within various tissues and organs continues to emerge, so does their role in a number of pathological conditions including cancer, diabetic retinopathy, and neurological disorders. Here, we review vascular pericyte contributions to the development and remodeling of the microcirculation, with a focus on the local microenvironment during these processes. We discuss observations of their earliest involvement in vascular development and essential cues for their recruitment to the remodeling endothelium. Pericyte involvement in the angiogenic sprouting context is also considered with specific attention to crosstalk with endothelial cells such as through signaling regulation and ECM deposition. We also address specific aspects of the collective cell migration and dynamic interactions between pericytes and endothelial cells during angiogenic sprouting. Lastly, we discuss pericyte contributions to mechanisms underlying the transition from active vessel remodeling to the maturation and quiescence phase of vascular development.

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“…Vascular PCs establish non-overlapping domains on vessels throughout the microcirculation (Grant et al, 2017) and have several established and proposed roles, such as blood flow regulation (Hall et al, 2014;Hill et al, 2015), shaping the extracellular matrix (ECM) surrounding blood vessels (Fernandez-Klett et al, 2013;Sava et al, 2015), and enhancing endothelial cell (EC) junction formation (Jo et al, 2013), in normal and pathological environments. These functions promote and maintain vascular integrity of established vasculature and thus, regulate vessel barrier function (von Tell et al, 2006;Winkler et al, 2018;Zhao et al, 2018). PCs directly interact with established endothelium via "peg-and-socket" adhesion molecules (Diaz-Flores et al, 2009) and intercellular communication channels of connexin-based gap junctions (GJs) (Fang et al, 2013;Hirschi et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Pericytes Directly Communicate with Emerging Endothelial Cells During Vasculogenesis

Payne

Tewari

Dunkenberger

et al. 2020

Preprint

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SummaryPericytes (PCs), cells that extend along capillaries to contribute stability and other critical functions to established vasculature, are attracting attention from various fields involving vascular-related pathologies. Here, we demonstrate primary evidence of PC communication with endothelial cells (ECs) prior to tube coalescence. Observations of apparent PCs during early embryogenesis urged development of a mouse embryonic stem cell line (DR-ESCs), enabling unique dual-reporter investigations into earliest PC-EC interactions. Live imaging of differentiating DR-ESCs corroborated emergence of a PC lineage, which preceded EC differentiation, and further revealed highly dynamic PC-EC interactions during coordinated vessel formation. We show direct PC-EC communication via cell microinjection and dye-transfer, and RNA-seq analysis indicates a PC-EC coupling mechanism via gap junction Connexin43 (Cx43), exclusively up-regulated throughout DR-ESC differentiation. High resolution imaging of embryonic and postnatal mouse vasculature substantiates Cx43 plaques at PC-EC borders. These findings indicate a new role for PCs during vasculogenesis via Cx43-mediated communication with ECs.

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Establishment and characterization of an embryonic pericyte cell line

Abstract: Our data support use of this pericyte cell line in a broad range of models to further understand pericyte functionality during normal and pathological conditions.

Cited by 13 publications

References 65 publications

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

The pericyte microenvironment during vascular development

Pericytes Directly Communicate with Emerging Endothelial Cells During Vasculogenesis

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