Adult neurogenesis in brain repair: cellular plasticity vs. cellular replacement

The last decade has seen an exponential increase in research directed to the field of regenerative medicine aimed at using stem cells in the repair of damaged organs including the brain. The therapeutic use of stem cells for neurological disorders includes either the modulation of endogenous stem cells resident in the brain or the introduction of exogenous stem cells into the brain. The final goal of these attempts is to replace damaged dysfunctional cells with new functional neurons. Nevertheless, there are multiple concerns regarding the therapeutic efficacy of the cellular replacement approach both from endogenous and exogenous sources. Indeed the extensive heterogeneity of neuronal subtypes in the brain makes it difficult to drive stem cells to differentiate to specific neuronal subtypes (Hawrylycz et al., 2012), which is a major requirement for regaining the lost neurological function. Furthermore, the fact that the brain is a very complex 3D structure with highly complex hierarchically organized connections raises a question on whether new neurons formed outside the brain niche can be functionally integrated into the preexisting circuitry. An alternative approach to cellular replacement can be enhancing plasticity in newborn neurons in the neurogenic niche to take over a function of a remote brain region. This strategy may have a yet unknown potential as it overcomes the limitations of the cellular replacement approach. In this opinion paper, we discuss limitations and potential of cellular replacement and cellular plasticity in the context of brain repair with a special focus on remote plasticity.

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