Date of Award

2012

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Social Work

Abstract

Capillaries are comprised of two cell types: the endothelial cells (ECs) which line the lumen of the capillary, and the supporting pericytes which are closely apposed to the abluminal surface of the capillary wall (sometimes called mural cells). These pericytes are phenotypic derivations of mesenchymal organ stromal cells (from smooth muscle cells and fibroblasts in blood vessels, for example), are recruited and incorporate into the neocapillaries, and are known to mediate reciprocal interactions with ECs during angiogenesis. The overall purpose of this project is to determine how smooth muscle cells (SMCs) affect angiogenesis during microvascular development in fibrin hydrogels using 3-dimensional co-culture models of angiogenesis. These studies are meant to model angiogenic processes in the wall of a fibrin-based tissue engineered blood vessel containing ECs and SMCs. Our results demonstrate that SMCs augment both the induction of angiogenesis and the persistence of capillary networks engineered ex vivo in fibrin hydrogels. This is in part mediated by the release of soluble factors into the extracellular environment that promote endothelial cell proliferation, migration, Erk activation, and Akt deactivation. Active Notch signaling in ECs is required for the SMC mediated induction of angiogenesis and deactivation of Akt. In conclusion, we have demonstrated a novel method with which to engineer microvasculatures in 3-D biologic scaffolds. The mediation of the pro-angiogenic effects of SMCs on angiogenesis by the Notch signaling pathway offers a potential therapeutic strategy for the modulation of tissue engineered microvasculatures.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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