Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Lauren Flynn

2nd Supervisor

Dr. David Hess

Joint Supervisor

Abstract

Stem cell transplantation is under investigation to stimulate angiogenesis in patients with peripheral artery disease. To develop a cell-delivery platform that enhances cell retention and function post-transplantation, the response of human adipose-derived stem/stromal cells (ASCs) encapsulated within N-methacrylate glycol chitosan (MGC) hydrogels with or without integrin-binding RGD or IKVAV motifs was explored. ASC viability was enhanced in the MGC and MGC-RGD hydrogels relative to the MGC-IKVAV group under hypoxic (2% O­2) culture conditions, with cell spreading and higher metabolic activity noted in MGC-RGD at 14 days. Analysis of angiogenic gene expression revealed similar patterns between all hydrogel groups, with higher levels of the pro-angiogenic factors HGF, VEGFA, ANGPTL4 and ANGPT2 in 3-D versus 2-D cultures. Characterization of the in vivo response following subcutaneous implantation in NOD/SCID mice showed enhanced ASC retention in MGC-RGD, with increased peri-implant CD31+ cell recruitment in the ASC-seeded MGC and MGC-RGD hydrogels relative to unseeded controls.

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