Dataset Information

Endothelial Cells Exposed to Fluid Shear Stress Support Diffusion Based Maturation of Adult Neural Progenitor Cells.

ABSTRACT:

Introduction

The neural stem cell (NSC) niche is a highly complex cellular and biochemical milieu supporting proliferating NSCs and neural progenitor cells (NPCs) with close apposition to the vasculature, primarily comprised of endothelial cells (ECs). Current in vitro models of the niche incorporate EC-derived factors, but do not reflect the physiologically relevant hemodynamic state of the ECs or the spatial resolution observed between cells within the niche.

Methods

In this work, we developed a novel in vitro model of the niche that (1) incorporates ECs cultured with fluid shear stress and (2) fosters paracrine cytokine gradients between ECs and NSCs in a spatiotemporal configuration mimicking the cytoarchitecture of the subventricular niche. A modified cone and plate viscometer was used to generate a shear stress of 10 dynes cm^-2 for ECs cultured on a membrane, while statically cultured NPCs are 10 or 1000 ?m below the ECs.

Results

NPCs cultured within 10 ?m of dynamic ECs exhibit increased PSA-NCAM⁺ and OLIG2⁺ cells compared to progenitors in all other culture regimes and the hemodynamic EC phenotype results in distinct progeny phenotypes. This co-culture regime yields greater release of pro-neurogenic factors, suggesting a potential mechanism for the observed progenitor maturation.

Conclusions

Based on these results, models incorporating ECs exposed to shear stress allow for paracrine signaling gradients and regulate NPC lineage progression with appropriate niche spatial resolution occurring at 10 ?m. This model could be used to evaluate cellular or pharmacological interactions within the healthy, diseased, or aged brain.

SUBMITTER: Dumont CM

PROVIDER: S-EPMC6816782 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Publications

Endothelial Cells Exposed to Fluid Shear Stress Support Diffusion Based Maturation of Adult Neural Progenitor Cells.

Dumont C M CM Piselli J J Temple S S Dai G G Thompson D M DM

Cellular and molecular bioengineering 20171201 2

<h4>Introduction</h4>The neural stem cell (NSC) niche is a highly complex cellular and biochemical milieu supporting proliferating NSCs and neural progenitor cells (NPCs) with close apposition to the vasculature, primarily comprised of endothelial cells (ECs). Current <i>in vitro</i> models of the niche incorporate EC-derived factors, but do not reflect the physiologically relevant hemodynamic state of the ECs or the spatial resolution observed between cells within the niche.<h4>Methods</h4>In t ...[more]

PMID: 31719881

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Project description:Blood flow produces mechanical frictional forces, parallel to the blood flow exerted on the endothelial wall of the vessel, the so-called wall shear stress (WSS). WSS sensing is associated with several vascular pathologies, but it is first a physiological phenomenon. Endothelial cell sensitivity to WSS is involved in several developmental and physiological vascular processes such as angiogenesis and vascular morphogenesis, vascular remodeling, and vascular tone. Local conditions of blood flow determine the characteristics of WSS, i.e., intensity, direction, pulsatility, sensed by the endothelial cells that, through their effect of the vascular network, impact WSS. All these processes generate a local-global retroactive loop that determines the ability of the vascular system to ensure the perfusion of the tissues. In order to account for the physiological role of WSS, the so-called shear stress set point theory has been proposed, according to which WSS sensing acts locally on vessel remodeling so that WSS is maintained close to a set point value, with local and distant effects of vascular blood flow. The aim of this article is (1) to review the existing literature on WSS sensing involvement on the behavior of endothelial cells and its short-term (vasoreactivity) and long-term (vascular morphogenesis and remodeling) effects on vascular functioning in physiological condition; (2) to present the various hypotheses about WSS sensors and analyze the conceptual background of these representations, in particular the concept of tensional prestress or biotensegrity; and (3) to analyze the relevance, explanatory value, and limitations of the WSS set point theory, that should be viewed as dynamical, and not algorithmic, processes, acting in a self-organized way. We conclude that this dynamic set point theory and the biotensegrity concept provide a relevant explanatory framework to analyze the physiological mechanisms of WSS sensing and their possible shift toward pathological situations.

Dataset Information

Endothelial Cells Exposed to Fluid Shear Stress Support Diffusion Based Maturation of Adult Neural Progenitor Cells.

Introduction

Methods

Results

Conclusions

Publications

Endothelial Cells Exposed to Fluid Shear Stress Support Diffusion Based Maturation of Adult Neural Progenitor Cells.

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