Optogenetics in stem cell research: Focus on the central nervous system
Stem cell-based therapies of CNS disorders represent a promising approach in translational and regenerative medicine. Stem cell-based tissue replacement and regeneration would, for the first time, offer a causal treatment strategy which is most likely not bound to a specific time window. Therapeutic strategies relying on this paradigm would require administration of exogenous stem cells to the CNS and/or the augmentation of endogenous stem cell capabilities. However, it remains unclear whether tissue replacement or bystander effects are required to induce such effects. Conventional experimental techniques will not be able to causally reveal such information, due to the complexity and coincidence of cellular processes and cell-target interactions, and the inability for longitudinal observations in vivo. Optogenetic approaches allow the targeted activation or inactivation of selected cell types, including stem cells. Optogenetics can therefore help to unravel the major th erapeutic mechanism of stem cell therapy in two ways: (1) to facilitate and improve neuronal differentiation of, e.g., ChR2 expressing stem cells and (2) to improve and test for functional integration of stem cell-derived neurons into the endogenous circuitry after transplantation. Here, we review the state of the art of optogenetic manipulation of stem cells to optimize therapeutic utilization for CNS disorders with a particular focus on endogenous and exogenous stem cell populations.