Electronic Thesis and Dissertation Repository

The effects of decellularized adipose tissue constructs on mesenchymal stromal/stem cell phenotype and pro-angiogenic secretory function.

Yehia Moharrem, The University of Western Ontario

Abstract

Due to limited treatment options for critical limb ischemia (CLI), cellular-based therapies have been investigated to induce blood vessel regeneration. Bone marrow-mesenchymal stromal/stem cells (BM-MSC) have shown pre-clinical success in animal models of CLI as they possess pro-angiogenic and immunomodulatory functions. However, clinical translation has been hindered by inadequate expansion and delivery strategies. This project aimed to characterize the phenotype and pro-angiogenic secretory function of BM-MSC on decellularized adipose tissue (DAT) bioscaffolds as expansion platforms. Compared to cells grown on tissue-culture plastic, DAT substrates supported BM-MSC growth, regenerative marker expression, and pro-angiogenic secretory function. Conditioned media generated by BM-MSC cultured on DAT coatings were enriched with factors associated with wound healing and significantly increased human endothelial cell survival under serum-free conditions in vitro. Overall, these studies show that DAT constructs present a promising tissue engineering approach to expand MSC while enhancing regenerative potential.