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Bioengineering Vascular Networks to Study Angiogenesis and Vascularization of Physiologically Relevant Tissue Models in Vitro.

ABSTRACT: Angiogenesis assays are essential for studying aspects of neovascularization and angiogenesis and investigating drugs that stimulate or inhibit angiogenesis. To date, there are several in vitro and in vivo angiogenesis assays that are used for studying different aspects of angiogenesis. Although in vivo assays are the most representative of native angiogenesis, they raise ethical questions, require considerable technical skills, and are expensive. In vitro assays are inexpensive and easier to perform, but the majority of them are only two-dimensional cell monolayers which lack the physiological relevance of three-dimensional structures. Thus, it is important to look for alternative platforms to study angiogenesis under more physiologically relevant conditions in vitro. Accordingly, in this study, we developed polymeric vascular networks to be used to study angiogenesis and vascularization of a 3D human skin model in vitro. Our results showed that this platform allowed the study of more than one aspect of angiogenesis, endothelial migration and tube formation, in vitro when combined with Matrigel. We successfully reconstructed a human skin model, as a representative of a physiologically relevant and complex structure, and assessed the suitability of the developed in vitro platform for studying endothelialization of the tissue-engineered skin model.

SUBMITTER: Dikici S

PROVIDER: S-EPMC7304666 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Bioengineering Vascular Networks to Study Angiogenesis and Vascularization of Physiologically Relevant Tissue Models in Vitro.

Dikici Serkan S Claeyssens Frederik F MacNeil Sheila S

ACS biomaterials science & engineering 20200429 6

Angiogenesis assays are essential for studying aspects of neovascularization and angiogenesis and investigating drugs that stimulate or inhibit angiogenesis. To date, there are several in vitro and in vivo angiogenesis assays that are used for studying different aspects of angiogenesis. Although in vivo assays are the most representative of native angiogenesis, they raise ethical questions, require considerable technical skills, and are expensive. In vitro assays are ...[more]

PMID: 32582840

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Project description:The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.

Dataset Information

Bioengineering Vascular Networks to Study Angiogenesis and Vascularization of Physiologically Relevant Tissue Models in Vitro.

Publications

Bioengineering Vascular Networks to Study Angiogenesis and Vascularization of Physiologically Relevant Tissue Models <i>in Vitro</i>.

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