Journal
INTEGRATIVE BIOLOGY
Volume 7, Issue 4, Pages 454-466Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5ib00052a
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Funding
- US National Institutes of Health (NIH) [RC1 CA146065]
- US National Institutes of Health (NIH) (Cornell Center on the Microenvironment and Metastasis) [NCI-U54 CA143876]
- Human Frontiers in Science Program
- Cornell Nanobiotechnology Center [NSF-STC
- ECS-9876771]
- Cornell Center for Nanoscale Science and Technology [NSF-NNIN ECS 03-35765]
- Empire State Development Division of Science, Technology and Innovation (NYSTAR) Center for Advanced Technology (CAT) award
- Sloan Foundation
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Vascular anastomosis - the fusion of vessels from two distinct branches of the vascular system - represents a critical step in vascular growth under both healthy and pathological conditions, in vivo, and presents an important target for engineering of vascularized tissues, in vitro. Recent works in animal models have advanced our understanding of the molecular and cellular players in vascular anastomosis, but questions remain related to cellular dynamics and control of this process, in vitro. In this study, we exploited a three-dimensional (3-D) culture platform to examine the dynamics of endothelial cell (EC) during and after vascular anastomosis by allowing angiogenesis and vasculogenesis to proceed in parallel. We show that anastomosis occurs between sprouts formed by angiogenesis from an endothelium and tubes formed by vasculogenesis in the bulk of a 3-D matrix. This fusion leads to highly connected vessels that span from the surface of the matrix into the bulk in a manner that depends on cell density and identity. Further, we observe and analyze intermixing of endothelial cells of distinct origin (surface versus bulk) within the vessels structures that are formed; we provide evidence that the cells migrate along pre-existing vessels segments as part of this intermixing process. We conclude that anastomosis can occur between vessels emerging by angiogenesis and vasculogenesis and that this process may play an important role in contexts such as wound healing.
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