Format

Send to

Choose Destination
Biomaterials. 2020 Jan;228:119554. doi: 10.1016/j.biomaterials.2019.119554. Epub 2019 Oct 18.

Microvascular engineering: Dynamic changes in microgel-entrapped vascular cells correlates with higher vasculogenic/angiogenic potential.

Author information

1
i3S - Instituto de Inovação e Investigação em Saúde, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
2
i3S - Instituto de Inovação e Investigação em Saúde, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
3
Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
4
i3S - Instituto de Inovação e Investigação em Saúde, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal. Electronic address: ccbarrias@ineb.up.pt.

Abstract

Successful strategies to promote neovascularization of ischemic tissues are still scarce, being a central priority in regenerative medicine. Microparticles harboring primitive vascular beds are appealing cell delivery candidates for minimally-invasive therapeutic vascularization. However, dynamic cellular alterations associated with in vitro vascular morphogenesis are still elusive. Here, bioengineered microgels guided the assembly of entrapped outgrowth endothelial cells (OEC) and mesenchymal stem cells (MSC) into cohesive vascularized microtissues. During in vitro maturation, OEC formed capillary-like networks enveloped in newly-formed extracellular matrix. Gene expression profiling showed that OEC acquired a mesenchymal-like phenotype, suggesting the occurrence of partial endothelial-to-mesenchymal transition (EndMT), while MSC remained transcriptionally stable. The secretome of entrapped cells became more pro-angiogenic, with no significant alterations of the inflammatory profile. Importantly, matured microgels showed improved cell survival/retention after transplantation in mice, with preservation of capillary-like networks and de novo formation of human vascular structures. These findings support that in vitro priming and morphogenesis of vessel-forming cells improves their vasculogenic/angiogenic potential, which is of therapeutic relevance, shedding some light on the associated mechanisms.

KEYWORDS:

Cell entrapment; Cell therapy; Injectable biomaterial; Morphogenesis; Tissue engineering; Vascular diseases

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center