Abstract

Mechanotransduction and Redox Regulation of Stem Cells

Thasaneeya Kuboki, Assistant Professor, Kyushu University

Mesenchymal stem cells (MSCs) from bone marrow are widely used in therapeutic applications due to their differentiation potency. However, the difficulties in the maintenance and expansion are the main challenges that impede their applications in tissue engineering and regenerative medicine. The tight control of stem cell microenvironment including the metabolic and mechanical environments is required to maintain their metabolism and physiology. Evidences suggested that the stiffness of underlying substrate mimic that of native tissues can direct stem cell lineage specification. Our previous proteomic analysis of MSCs on different elasticity gels revealed the differential expression of intracellular signaling molecules including the antioxidant enzymes. In this study, the direct correlation of redox balance and stem cell fate in response to mechanical stimuli was evaluated using elasticity tunable gelatin hydrogel. We examined the production of Reactive oxygen species (ROS), nuclear localization of transcription factors that regulate antioxidant response, mRNA expression of differentiation markers and antioxidant genes in MSCs on substrates with different surface elasticity. The data indicated that the mechanical stimuli from the underlying substrates could modulate the cellular redox balance, ROS production and expression of the lineage specific markers of the stem cells, reflecting the crosstalk between mechanotransduction and redox signaling.