Surface stiffness depended gingival mesenchymal stem cell sensitivity to oxidative stress

Abstract

Mesenchymal stem cells (MSCs) are widely used in the fields of cell therapy and tissue engineering, due to their wide spectrum of differentiation potential, immunomodulation function and ongoing oxidative stress (OS) reduction. Nevertheless, OS impact is often overlooked in these research fields. It is not only responsible for the induction and development of many ailments, e.g., diabetes, lung fibrosis, and cancer, moreover, OS causes stem cell death and senescence during cell therapy and tissue engineering practices. As MSCs are used to treat various tissues, they interact with different tissue-specific mechanical environments, thus it is important to understand how the mechanical environment impacts MSC sensitivity to OS. In this work, for the first time, as known to the authors, it was shown that gingival MSCs (GMSCs) sensitivity to OS depends on the stiffness of the surface, on which the cells are grown. Furthermore, the activity and expression of mitogen activated protein kinases ERK, JNK, and p38 were surface stiffness dependent. GMSCs isolated from intermediate/stiff gingiva tissue (~20 kPa) have shown the best proliferative and survival properties, then grown on the stiffest tissues mimicking polyacrylamide hydrogels (40 kPa). Therefore, MSC source might determine their sensitivity to OS in different stiffness environments and should be accounted when developing a treatment strategy.

Keywords: Gingival mesenchymal stem cells (GMSC); Hydrogen peroxide; Mechanical environment; Mitogen activated protein kinases (MAPK); Oxidative stress (OS); Stiffness.