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Issue 1, 2015
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Locally controlling mesenchymal stem cell morphogenesis by 3D PDGF-BB gradients towards the establishment of an in vitro perivascular niche

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Abstract

The perivascular niche is a complex microenvironment containing mesenchymal stem cells (MSCs), among other perivascular cells, as well as temporally organized biochemical and biophysical gradients. Due to a lack of conclusive phenotypic markers, MSCs' identity, heterogeneity and function within their native niche remain poorly understood. The in vitro reconstruction of an artificial three-dimensional (3D) perivascular niche would offer a powerful alternative to study MSC behavior under more defined conditions. To this end, we here present a poly(ethylene glycol)-based in vitro model that begins to mimic the spatiotemporally controlled presentation of biological cues within the in vivo perivascular niche, namely a stably localized platelet-derived growth factor B (PDGF-BB) gradient. We show that 3D-encapsulated MSCs respond to soluble PDGF-BB by proliferation, spreading, and migration in a dose-dependent manner. In contrast, the exposure of MSCs to 3D matrix-tethered PDGF-BB gradients resulted in locally restricted morphogenetic responses, much as would be expected in a native perivascular niche. Thus, the herein presented artificial perivascular niche model provides an important first step towards modeling the role of MSCs during tissue homeostasis and regeneration.

Graphical abstract: Locally controlling mesenchymal stem cell morphogenesis by 3D PDGF-BB gradients towards the establishment of an in vitro perivascular niche

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Supplementary files

Article information


Submitted
01 Jul 2014
Accepted
24 Oct 2014
First published
28 Oct 2014

Integr. Biol., 2015,7, 101-111
Article type
Paper
Author version available

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