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University of Texas – Austin

1. -9024-5383. Glypican-1 proteoliposomes enhance growth factor activity for therapeutic angiogenesis.

Degree: Biomedical Engineering, 2018, University of Texas – Austin

Peripheral arterial disease affects more than 27 million patients in the United States. PAD can lead to peripheral limb ischemia and result in non-healing foot ulcers. Currently, surgical therapies such a stenting, grafting, and bypass, exist for treatment of ischemia, but these treatments are prone to long-term failure. These treatments also only successfully yield beneficial results about 25% of the time. Alternatively, regenerative therapies that stimulate the growth of new vasculature have great potential for treating peripheral and myocardial ischemia. Growth factor based therapies that induce neovascularization have shown promising results in animal models, but have limited success in clinical trials. This discrepancy is most likely a result of growth factor resistance brought on by diseases that lead to peripheral vascular disease. Here, we have developed a new method for enhancing the activity of growth factors in growth factor resistant disease states such as diabetes and hyperlipidemia. Our novel method delivers the growth factor co-receptor glypican-1 embedded in a liposomal carrier to create a glypican-1 proteoliposome (a “glypisome”). By co-delivering the co-receptor glypican-1 along with the growth factor, we hope to overcome growth factor resistance associated with long-term disease. Here we optimize glypisome composition to maximize angiogenic response when co-delivered with growth factors, through the use of in vitro endothelial assays and explore what mechanisms bring about this change in activity. Then we determine therapeutic potential of co-delivering glypisomes with growth factors in vivo by assessing neovascularization in healthy and disease mouse models of ischemia. We also explore overcoming disease mediated growth factor resistance by delivering glioblastoma-derived exosomes as a naturally occurring alternative to the glypisomes that we have developed. We test these exosomes in both in vitro endothelial assays and in vivo with a mouse hind limb ischemia model. We demonstrate that delivering these co-receptors in conjunction with the growth factor will allow us to overcome the disease phenotype and lead to a viable growth factor therapy for peripheral arterial disease. Advisors/Committee Members: Baker, Aaron Blair (advisor), Dunn, Andrew K (committee member), Mukhopadhyay, Somshuvra (committee member), Stachowiak, Jeanne (committee member), Suggs, Laura (committee member).

Subjects/Keywords: Glypican-1; FGF-2; VEGF; Ischemia; Angiogenesis; Growth factor

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APA (6th Edition):

-9024-5383. (2018). Glypican-1 proteoliposomes enhance growth factor activity for therapeutic angiogenesis. (Thesis). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/68372

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

-9024-5383. “Glypican-1 proteoliposomes enhance growth factor activity for therapeutic angiogenesis.” 2018. Thesis, University of Texas – Austin. Accessed October 19, 2018. http://hdl.handle.net/2152/68372.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

-9024-5383. “Glypican-1 proteoliposomes enhance growth factor activity for therapeutic angiogenesis.” 2018. Web. 19 Oct 2018.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

-9024-5383. Glypican-1 proteoliposomes enhance growth factor activity for therapeutic angiogenesis. [Internet] [Thesis]. University of Texas – Austin; 2018. [cited 2018 Oct 19]. Available from: http://hdl.handle.net/2152/68372.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

-9024-5383. Glypican-1 proteoliposomes enhance growth factor activity for therapeutic angiogenesis. [Thesis]. University of Texas – Austin; 2018. Available from: http://hdl.handle.net/2152/68372

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

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