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Engineering of an angiogenic niche by perfusion culture of adipose-derived stromal vascular fraction cells

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Cerino Giulia, Gaudiello Emanuele, Muraro Manuele Giuseppe, Eckstein Friedrich, Martin Ivan, Scherberich Arnaud, Marsano Anna,
Project Engineered patches for cardiac repair
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Original article (peer-reviewed)

Journal Scientific Reports
Volume (Issue) 7(1)
Page(s) 14252 - 14252
Title of proceedings Scientific Reports
DOI 10.1038/s41598-017-13882-3

Open Access

URL http://doi.org/10.1038/s41598-017-13882-3
Type of Open Access Publisher (Gold Open Access)

Abstract

In vitro recapitulation of an organotypic stromal environment, enabling efficient angiogenesis, is crucial to investigate and possibly improve vascularization in regenerative medicine. Our study aims at engineering the complexity of a vascular milieu including multiple cell-types, a stromal extracellular matrix (ECM), and molecular signals. For this purpose, the human adipose stromal vascular fraction (SVF), composed of a heterogeneous mix of pericytes, endothelial/stromal progenitor cells, was cultured under direct perfusion flow on three-dimensional (3D) collagen scaffolds. Perfusion culture of SVF-cells reproducibly promoted in vitro the early formation of a capillary-like network, embedded within an ECM backbone, and the release of numerous pro-angiogenic factors. Compared to static cultures, perfusion-based engineered constructs were more rapidly vascularized and supported a superior survival of delivered cells upon in vivo ectopic implantation. This was likely mediated by pericytes, whose number was significantly higher (4.5-fold) under perfusion and whose targeted depletion resulted in lower efficiency of vascularization, with an increased host foreign body reaction. 3D-perfusion culture of SVF-cells leads to the engineering of a specialized milieu, here defined as an angiogenic niche. This system could serve as a model to investigate multi-cellular interactions in angiogenesis, and as a module supporting increased grafted cell survival in regenerative medicine.
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