Prospects for engineering neurons from local neocortical cell populations as cell-mediated therapy for neurological disorders.
There is little cell replacement following neurological injury, limiting the regenerative response of the CNS. Progress in understanding the biology of neural stem cells has raised interest in using stem cells for replacing neurons lost to injury or to disease. Stem cell therapy may also have a role in rebuilding deficient neural circuitry underlying mood disorders, epilepsy, and pain modulation among other roles. In vitro expansion of stem cells with directed differentiation prior to transplantation is one approach to stem cell therapy. Emerging evidence suggests that it may be possible to convert in vivo endogenous neural cells to a neuronal fate directly, providing an alternative strategy for stem cell therapy to the CNS. This review assesses the evidence for engineering a subtype-specific neuronal fate of endogenous neural cells in the cerebral cortex as a function of initial cell lineage, reactive response to injury, conversion factors, and environmental context. We conclude with a discussion of some of the challenges that must be overcome to move this alternative in vivo engineered conversion process toward becoming a viable therapeutic option.
Center for Stem Cell and Regenerative Medicine, Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, 60064.
Stanley
S
Bazarek
Daniel A
DA
Peterson
D000818:Animals; D002454:Cell Differentiation; D060846:Cell Engineering; D006801:Humans; D019579:Neocortex / Q000166:cytology*; D009422:Nervous System Diseases / Q000628:therapy*; D058953:Neural Stem Cells / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*
direct in vivo conversion; endogenous recruitment; injury-induced neurogenesis; neural stem cell; neuronal replacement; reprogramming