Investigation of Chitosan-based Hydrogels as a Cell Delivery Platform for Adipose-derived Stem/Stromal Cell Transplantation to Promote Angiogenesis in Ischemic Tissues
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.