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Angiogenic Factors produced by Hypoxic Cells are a leading driver of Anastomoses in Sprouting Angiogenesis-a computational study.

ABSTRACT: Angiogenesis - the growth of new blood vessels from a pre-existing vasculature - is key in both physiological processes and on several pathological scenarios such as cancer progression or diabetic retinopathy. For the new vascular networks to be functional, it is required that the growing sprouts merge either with an existing functional mature vessel or with another growing sprout. This process is called anastomosis. We present a systematic 2D and 3D computational study of vessel growth in a tissue to address the capability of angiogenic factor gradients to drive anastomosis formation. We consider that these growth factors are produced only by tissue cells in hypoxia, i.e. until nearby vessels merge and become capable of carrying blood and irrigating their vicinity. We demonstrate that this increased production of angiogenic factors by hypoxic cells is able to promote vessel anastomoses events in both 2D and 3D. The simulations also verify that the morphology of these networks has an increased resilience toward variations in the endothelial cell's proliferation and chemotactic response. The distribution of tissue cells and the concentration of the growth factors they produce are the major factors in determining the final morphology of the network.

SUBMITTER: Moreira-Soares M

PROVIDER: S-EPMC5992150 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Angiogenic Factors produced by Hypoxic Cells are a leading driver of Anastomoses in Sprouting Angiogenesis-a computational study.

Moreira-Soares Maurício M Coimbra Rita R Rebelo Luís L Carvalho João J D M Travasso Rui R

Scientific reports 20180607 1

Angiogenesis - the growth of new blood vessels from a pre-existing vasculature - is key in both physiological processes and on several pathological scenarios such as cancer progression or diabetic retinopathy. For the new vascular networks to be functional, it is required that the growing sprouts merge either with an existing functional mature vessel or with another growing sprout. This process is called anastomosis. We present a systematic 2D and 3D computational study of vessel growth in a tis ...[more]

PMID: 29880828

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Project description:Tissue regeneration or healing both require efficient vascularization within a tissue-damaged area. Based on this concept, a remarkable number of strategies, aimed at developing new tools to support re-vascularization of damaged tissue have emerged. Among the strategies proposed, the use of pro-angiogenic soluble factors, as a cell-free tool, appears as a promising approach, able to overcome the issues concerning the direct use of cells for regenerative medicine therapy. Here, we compared the effectiveness of adipose mesenchymal stem cells (ASCs), use as cell suspension, ASC protein extract or ASC-conditioned-medium (i.e., soluble factors), combined with collagenic scaffold, in supporting in vivo angiogenesis. We also tested the capability of hypoxia in increasing the efficiency of ASC to promote angiogenesis, via soluble factors, both in vivo and in vitro. In vivo studies were performed using the Integra® Flowable Wound Matrix, and the Ultimatrix in sponge assay. Flow cytometry was used to characterize the scaffold- and sponge-infiltrating cells. Real-time PCR was used to evaluate the expression of pro-angiogenic factors by stimulating Human Umbilical-Vein Endothelial Cells with ASC-conditioned media, obtained in hypoxic and normoxic conditions. We found that, in vivo, ACS-conditioned media can support angiogenesis similar to ASCs and ASC protein extract. Also, we observed that hypoxia increases the pro-angiogenic activities of ASC-conditioned media, compared to normoxia, by generating a secretome enriched in pro-angiogenic soluble factors, with bFGF, Adiponectine, ENA78, GRO, GRO-a, and ICAM1-3, as most regulated factors. Finally, ASC-conditioned media, produced in hypoxic condition, induce the expression of pro-angiogenic molecules in HUVECs. Our results provide evidence that ASC-conditioned-medium can be proposed as a cell-free preparation able to support angiogenesis, thus providing a relevant tool to overcome the issues and restrictions associated with the use of cells.

Dataset Information

Angiogenic Factors produced by Hypoxic Cells are a leading driver of Anastomoses in Sprouting Angiogenesis-a computational study.

Publications

Angiogenic Factors produced by Hypoxic Cells are a leading driver of Anastomoses in Sprouting Angiogenesis-a computational study.

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