In vivo and in vitro, biophysical cues in the extracellular matrix (ECM) play vital roles in regulating stem cell behavior. In living organisms, the ECM is comprised of micro and nanoscaled topographical features that interact with cells and define their behavior and fate. This relationship provides a rationale for developing artificial architectures that compose micro and nanoscaled topographical features to mimic the natural ECM. However, existing fabrication methods (i.e. photolithography) failed to provide a finely tunable and cost-effective way to generate hierarchical architectures consisting of micro and nanoscaled topography. Our metal electrodeposition approach is a highly tunable process that offers direct fabrication of hierarchical architectures with precisely defined micro and nanoscaled topography. Here, we utilized this highly tunable platform to guide the differentiation of human mesenchymal stem cells (hMSCs) toward neural lineage.[1] The hierarchical architectures efficiently upregulated the neuronal differentiation of hMSCs cells. Remarkably, we observed that the surface morphology of the architectures is a key regulator for promoting the neural differentiation. The enrichment in nanoscaled topographical features dramatically increased the interaction between hMSCs and architectures and promoted the formation of filopodia, an essential membrane protrusion in developing neurons. We further quantified the degree of neural differentiation via immunostaining and qPCR. At the protein level, 85% of the differentiated hMSCs expressed microtubule-associated protein 2 (MAP2), a mature neural marker after seven days of culture. At the mRNA level, the differentiated hMSCs have comparable a MAP2 expression to in vitro neuroblastomas. Taken together, mature neural cells can be achieved after seven days of culture in the hierarchical architectures without the presence of any soluble factors. Our finding suggests that nanoscale microenvironment plays a critical role in defining stem cell fate and can be utilized to facilitate the production of differentiated stem cells for regenerative medicine.

Three-dimensional nanostructured architectures enable efficient neural differentiation of mesenchymal stem cells via mechanotransduction

2019 Spring National Meeting

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