Mesenchymal Stem Cell Behavior on Soft Hydrogels with Aligned Surface Topographies

Human mesenchymal stem cells (HMSCs) are important for cell-based therapies. However, the success of HMSC therapy requires large-scale in vitro expansion of these multipotent cells. The traditional expansion of HMSCs on tissue-culture-treated stiff polystyrene induces significant changes in their shape, multipotency, and secretome, leading to early senescence and subdued paracrine activity. To enhance their therapeutic potential, here, we have developed two-dimensional soft hydrogels with imprinted microscale aligned grooves for use as HMSC culture substrates. We showed that, depending on the dimensions of the topographical features, these substrates led to lower cellular spreading and cytoskeletal tension, maintaining multipotency and osteogenic and adipogenic differentiate potential, while lowering cellular senescence. We also observed a greater capacity of HMSCs to produce anti-inflammatory cytokines after short-term priming on these hydrogel substrates. Overall, these soft hydrogels with unique surface topography have shown great promise as in vitro culture substrates to maximize the therapeutic potential of HMSCs.

Automated summary

In this study, two-dimensional soft hydrogels with microscale aligned grooves were developed as culture substrates for human mesenchymal stem cells (HMSCs). The topographical features of the hydrogel surface led to reduced cellular spreading and senescence, while maintaining the multipotency and differentiation potential of the cells. HMSCs cultured on these hydrogels also exhibited an increased capacity to produce anti-inflammatory cytokines. Overall, the soft hydrogels showed great promise for maximizing the therapeutic potential of HMSCs in vitro.