Continued and extensive progress in stem cell research in both basic and pre-clinical settings should support the hope for development of NSC-based therapies for neurodegenerative diseases. This review focuses on the utility of stem cells, particularly NSCs, as substrates for structural and functional repair Akt inhibitor of the diseased or injured brain. Parkinson’s disease, characterized by an extensive loss of dopamine (DA) neurons in the substantia nigra pars compacta and their terminals in the striatum,
affects more than 500 000 people in the US and about 50 000 new cases are reported annually.[20, 21] While the etiology of idiopathic PD is not known, several predisposing factors for the dopamine depletion associated with the disease have been suggested, including programmed cell death, viral infection, and environmental toxins. As an effective treatment for
PD, patients have been given L-dihydroxyphenyl alanine (L-DOPA), a precursor of dopamine, but long-term administration of L-DOPA consequently produces grave side effects.[22, 23] More recently, surgical deep brain stimulation has been adopted as a successful treatment for PD patients. Since the late 1980s, transplantation of human fetal ventral mesencephalic tissues into the striatum of PD patients has been used as a successful therapy for patients with advanced disease.[25-28] However, this fetal tissue transplantation has serious problems associated Small molecule high throughput screening with ethical and religious questions and logistics of acquiring fetal tissues. In addition, recent reports have indicated that the survival Isotretinoin of transplanted fetal mesencephalic cells in the patients’ brain was very low and it was difficult to obtain enough fetal tissues needed for transplantation. To circumvent these difficulties, utilization of neurons with dopaminergic (DA) phenotype generated from ESCs, iPSCs, MSCs or NSCs could serve as a practical and effective alternative for the fetal brain tissues
for transplantation. DA neurons were generated from mouse ESCs after treatment with fibroblast growth factor 8 (FGF8) and sonic hedgehog,[30, 31] over-expression of Nurr1[32, 33] or Bcl-XL, or co-culture with a mouse bone marrow stromal cell line. Neurons with DA phenotype have been generated from monkey ESCs by co-culturing with mouse bone marrow stromal cells and behavioral improvement was seen in MPTP-lesioned monkeys following intra-striatal transplantation of these cells. DA neurons were also generated from neural progenitor cells derived from fetal brain and induced functional recovery following brain transplantation in parkinsonian monkeys. Transplantation of NSCs in the brain attenuates anatomic or functional deficits associated with injury or disease in the CNS via cell replacement, the release of specific neurotransmitters, and the production of neurotrophic factors that protect injured neurons and promote neuronal growth.