Snyder EY, Macklis JD. Multipotent neural progenitor or stem-like cells may be uniquely suited for therapy for some neurodegenerative conditions. Clinical neuroscience (New York, N.Y.). 3(5):310-6. Pubmed: 8914798


Multipotent neural progenitors or stem cells (or cells which mimic their behavior) are capable of differentiating along multiple central nervous system (CNS) cell-type lineages, neuronal and glial. They can engraft as integral members of normal structures throughout the host CNS without disturbing other neurobiological processes. By exploiting their basic biologic properties, these cells may be able to disseminate therapeutic gene products in a sustained, direct fashion throughout the CNS. In addition, they may replace dysfunctional neurons and glia in both a site-specific and global manner. They may play a therapeutic role in neurodegenerative conditions that occur both during development and in the mature brain. The ability of neural stem cells to respond to neurogenic cues not only when they occur during their normal developmental expression but even when induced or "reactivated" at later stages following injury, may entrance their utility in reconstituting damaged CNS regions. Thus, these vehicles may overcome many of the limitations of viral and non-neural cellular vectors, as well as pharmacologic and genetic interventions. The feasibility of this broadly applicable neural stem cell-based strategy has been demonstrated in a number of murine models of neurodegenerative disease. The focus of this review will be our recent observation of a possible tropism of such cells for neurodegenerative environments.

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Jeffrey Macklis investigates molecular controls and mechanisms over neuron subtype specification, development, diversity, axon guidance-circuit formation, and pathology in the cerebral cortex. His lab seeks to apply developmental controls toward brain and spinal cord regeneration and directed differentiation for in vitro mechanistic modeling using human assembloids.

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