The growth of adipose tissue is tightly coupled with neovascularization. Understanding of such relationship is key for the design of anti-obesity therapeutics or conversely for the engineering of vascularized adipose tissue which could eventually serve as a material for use in the replacement of lost or damaged tissue due to tumor removal, trauma, lipoatrophy, or congenital defects. Although in vitro studies have led to the identification of many angiogenic factors in adipose tissue, as well as adipokines, there is still a paucity of knowledge about the dynamic relationship between adipocytes, stromal cells, and endothelial cells. In vivo animal studies have provided some insight into the concomitant process of angiogenesis and adipogenesis, but many of these models require translation to humans. In this proposed research training fellowship, the design of a novel 3D in vitro system with perfused human capillaries that can be useful for enhancing the fundamental understanding of these two processes is presented. For this system the fusion of microfabrication techniques with 3D cell culture will be used to create a microfludic device consisting of two fluid-filled microfabricated microchannels separated by metabolically active tissue. Once the device has been constructed and characterized, preadipocytes will be introduced into the microtissue and the simultaneous formation of angiogenesis with adipogenesis will be investigated. It is hypothesized that adipocytes can regulate new vasculature and participate in new vessel formation structurally, impacting both permeability and vessel growth
This research training proposal is driven by the objective of creating a 3D in vitro system with perfused human capillaries that will enhance the fundamental understanding of angiogenesis and adipogenesis. Obesity is a major risk factor for the development of many several prevalent and costly human diseases such as Type 2 diabetes, cardiovascular disease and cancer, all of which are linked to angiogenesis. The results of this proposal could facilitate the design of better therapies to reduce or cure obesity and its associated co- morbidities, and thus significantly reduce health care expenditures. .
|Alonzo, Luis F; Moya, Monica L; Shirure, Venktesh S et al. (2015) Microfluidic device to control interstitial flow-mediated homotypic and heterotypic cellular communication. Lab Chip 15:3521-9|
|Moya, Monica L; Hsu, Yu-Hsiang; Lee, Abraham P et al. (2013) In vitro perfused human capillary networks. Tissue Eng Part C Methods 19:730-7|
|Hsu, Yu-Hsiang; Moya, Monica L; Abiri, Parinaz et al. (2013) Full range physiological mass transport control in 3D tissue cultures. Lab Chip 13:81-9|
|Moya, Monica; Tran, David; George, Steven C (2013) An integrated in vitro model of perfused tumor and cardiac tissue. Stem Cell Res Ther 4 Suppl 1:S15|