Designer substrates to engineer stem cells secretome production

Abstract

Angiogenesis holds an important role in wound healing by constructing new blood vessels from the preexisting vessels through the invasion of injury clot. This process is largely regulated by signals from both the surrounding extracellular matrix (ECM) environment and serum. In hopes to have deeper understanding towards stem cells activity, hydrogels is often used in studies to biomimick ECM. In this study, fibronectin-conjugated polyacrylamide (PAA) hydrogel with adjustable stiffness is exploited to regulate the intracellular oxidative state of adipose derived stem cells (ADSCs). Our results have shown hydrogels of varied kPa stiffness increase the reactive oxidative species(ROS) levels in ADSCs as compared to ADSCs cultured on fibronectin coated glass slip control in an almost non-cytoxic way. The concoction of secreted proteins by ADSCs can be modulated by intracellular ROS levels via the adjustable hydrogel substrate stiffness. The secretome or conditioned medium(CM) retrieved from the ADSCs cultured on varied stiffness substrate, were thereafter cultured with human umbilical vein endothelial cells (HUVECs) and results have shown that the CM from ADSCs on the softest substrate promotes angiogenesis. Findings from this study shows that soft materials can be a novel approach to induce oxidative stress in MSCs to stimulate them to secrete pro-healing factors.