Parkinson's disease (PD), a prevalent geriatric neurodegenerative disorder, is characterized by selective dopaminergic
neuronal death in the substantia nigra, leading to motor and non-motor symptoms. Current therapeutic options
are limited to symptomatic relief that do not reverse the underlying pathology. Dopaminergic neural replacement through
grafting of fetal mesencephalic tissue, while promising in theory, has had many barriers to routine clinical use. Such tissue
survives and integrates poorly into recipients and has shown little benefit in sham-controlled surgical studies. Graftinduced
dyskinesias often result from immune rejection and bias for serotonergic neuronal differentiation. Pluripotent embryonic
stem cells (ES cells) are also theoretically promising but may form aberrant non-neural tissue and suffer graft rejection.
Neural stem cell (NSCs) are a subset of adult stem cells that are limited to neural tissue differentiation and may be
more easily expanded, integrated and regulated than fetal mesencephalic transplants or ES cells. Graft rejection and ethical
issues would complicate use of allogeneic fetal NSCs, however. It would also be unsafe to obtain NSCs directly from
patients given that they are present only within intricate brain regions and from adults have poor capacity for proliferation.
Thus, the future of neuroregenerative therapy for PD may lie in generation of NSCs from patient-derived induced pluripotent
stem cells (somatic cells artificially endowed with pluripotency) or endogenously increased by mitogenic drugs.
Overall, therapy for Parkinson’s disease should be long-term and safe while producing expandable, integrated, and phenotypically
Keywords: Induced pluripotent stem cells, mesenchymal stem cells, MS-818, neural stem cells, neurodegeneration, Parkinson’s
disease, regenerative therapy, stem cell therapy.
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