Combining Topographical and Genetic Cues to Promote Neuronal Fate Specification in Stem Cells

Abstract

There is little remedy for the devastating effects resulting from neuronal loss caused by neural injury or neurodegenerative disease. Reconstruction of damaged neural circuitry with stem cell-derived neurons is a promising approach to repair these defects, but controlling differentiation and guiding synaptic integration with existing neurons remain significant unmet challenges. Biomaterial surfaces can present nanoscale topographical cues which influence neuronal differentiation and process outgrowth. By combining these scaffolds with additional molecular biology strategies, synergistic control over cell fate can be achieved. Here, we review recent progress in promoting neuronal fate using techniques at the interface of biomaterial science and genetic engineering. New data demonstrates that combining nanofiber topography with an induced genetic program enhances neuritogenesis in a synergistic fashion. We propose combining patterned biomaterial surface cues with prescribed genetic programs to achieve neuronal cell fates with the desired sublineage specification, neurochemical profile, targeted integration and electrophysiological properties.

Soft Graphene Nanofibers Designed for the Acceleration of Nerve Growth and Development

“…However, interestingly, the electrical stimulation applied by the G-NFs did not cause an inhibitory effect on the replenishment of Ca 2+ store in cell membrane of the motor neurons in a long-term electrical stimulation of 3 d, which usually happened during the electrical stimulation applied by the 2D fi lm materials because of the cell adaptability to invariant stimulation location and electron charge density. [41][42][43] For instance, in this study, the promotion of the electrical stimulation applied by the G-fi lm (G-fi lm/ES) on cell growth and development only happened at the beginning of the electrical stimulation, which was similar or even better than that of the G-NFs. But, from the day 2 to day 3, the neurites elongation, sprouting, and cell maturation of the motor neurons on the TCP, G-fi lm and G-fi lm/ES were at the same level.…”

Silk nanofiber hydrogels with tunable modulus to regulate nerve stem cell fate

“…33–36 Different strategies encompassing physical approaches, architectural designs, bioactive molecule release, genetic engineering and synergism among these features have been evaluated to achieve control over cell fate. 4,41–45,57,58 …”

“…21–23 However, significant challenges remain to achieve desired neural cell fates by integrating different strategies in the biomaterials designs, including the choice of biomaterial, microstructural and mechanical features, and the incorporation of bioactive molecules. 4 …”

“…44 The combined control of rigidity and topography is also difficult because nanostructure fabrication usually requires higher stiffness than found in nerve tissues. 4 In order to overcome the problems of electrospun silk nanofibers used in neural regeneration, silk fibroin hydrogels with tunable stiffness have been developed to facilitate neural cell growth and tissue regeneration. 44 Unfortunately, ECM-mimic nanofiber fabrication is unfeasible for the silk hydrogel system.…”

A synthetic nanofibrillar matrix promotes in vitro hepatic differentiation of embryonic stem cells and induced pluripotent stem cells

“…In addition, the ECM was found to deposit as an extensive scaffold on the basal surface of the cells attached to NFs (Shih et al, 2006;Chua et al, 2007;Ma et al, 2008). Importantly, the sNF system has been reported to enhance not only the differentiation of murine ES cells into neural lineages (Lim et al, 2010;Purcell et al, 2012;Xie et al, 2009), but also differentiation from human MSCs into hepatoblasts (Ghaedi et al, 2012;Kazemnejad et al, 2009).…”