Electronic Thesis and Dissertation Repository

Development of a Tissue Specific Bioscaffold for Intestinal Stem Cell Culture

Sachin Kakar, The University of Western Ontario

Abstract

The generation of a tissue-specific intestinal hydrogel using small intestinal extracellular matrix (ECM) has the potential to support and promote the growth of intestinal organoids. In this study, we aimed to develop hydrogels derived exclusively from intestinal ECM or composites comprised of intestinal ECM combined with alginate, which may allow greater tuning of the hydrogel properties. A novel mouse intestinal decellularization protocol was developed and the ECM was characterized. Our analysis demonstrates that cellular and nuclear content was removed effectively, while preserving key ECM components. When decellularized ECM was used to generate hydrogels, the resulting ECM displayed bioactivity as demonstrated by metabolic and pro-proliferative effects on NIH 3T3 murine fibroblasts. More importantly, our novel ECM hydrogel also supported intestinal organoid growth. These studies demonstrate that tissue-specific ECM-derived hydrogels can indeed support and promote the growth of intestinal organoids in vitro.