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The mammalian adult brain is a regenerative system capable of incorporating embryonic stem (ES), progenitor, or fetal primary neurons into new circuitries. These implanted or regenerating neurons and glia grow to functionally repair damaged or degenerated neuronal connections. First, by transplanting immature neurons into various locations in the brain of animal models, we determined which connections and reparative interactions with the host are possible using fetal or ES cells. We found that implanted fetally derived or ES cell–derived dopamine neurons can survive in the long term, and gradually reduce signs of Parkinson disease in various animal-model systems. Second, the differentiation pathways and molecular switches necessary for specific dopamine cell identity and growth were evaluated. There are genetic modifications and trophic factor support involving Nurr1, PitX3, Shh, FGF8, and markers modifying growth-cone behaviors and cell type specification from ES to dopamine neurons. The presence of these factors can further enhance the restoration of normal neuronal dopamine function. The functional studies of neurodegenerative models and potential repair in Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis provide new opportunities for evaluating the therapeutic use of stem cells.
Isacson O. The Therapeutic Potential of Stem Cells for Nervous System Diseases. Arch Neurol. 2003;60(2):295. doi:10.1001/archneur.60.2.295-a
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