Topological defects induced intra-tissue heterogeneity of mesenchymal stem cell via regulatory self-organization and differentiation

Currently, in vitro fabrication of intra-tissue heterogeneity remains a critical challenge in development of adult stem cell based tissue engineering. Interestingly, as a typical structure in symmetry-breaking phase transitions, topological defects are extensively presented in biological substances. These topological defects are commonly observed within cell monolayer in vitro and demonstrated to be effective in induction of intra-tissue heterogeneity by regulating cell migration. Nevertheless, their impacts on the behavior of mesenchymal stem cells (MSCs) remain elusive. In this study, micro-grooved substrates were utilized to explore the role of topological defects in regulation of MSCs' self-organization and osteogenic differentiation. The results indicated that topological defects could induce the central aggregates of MSCs at central region of +1 and +1/2 topological defects by modulating centripetal migration. On the contrast, negatively charged topological were able to induce centrifugal migration and further inducing heterogeneous distribution of MSCs. Subsequently, these heterogeneously distributed MSCs were capable of inducing intra-tissue heterogeneity in terms of proliferation, stemness maintenance and osteogenic differentiation via regulatory morphogenesis.