Behavioral improvement in a primate Parkinsonís model is associated with multiple homeostatic effects of human neural stem cells.
Redmond, D.E., Bjugstad, K.B., Teng, Y.D., et al. Proc. Natíl Acad. Sci., 104, 12175-12180 (July 17, 2007)
Discovered decades ago, L-DOPA and other drugs that raise dopamine levels remain key elements in our pharmacopeia for Parkinsonís disease. More recently, attempts have been made to replace the lost neurons of the substantia nigra with fetal dopamine neurons, unfortunately with limited success. Results of the current paper suggest that pluripotent neural stem cells may constitute an alternative.
Using a primate model for Parkinsonís (treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or MPTP), the authors demonstrated that implantation of human neural stem cells into the substantia nigra and bilaterally into the caudate nucleus (1 million per site) significantly reduced the behavioral traits associated with the disease over a four-month period. A histological examination revealed that stem cells injected near the right substantia nigra migrated through the nigrostriatal pathway.
Histological examinations of the human neural stem cells at seven to eight months post-implantation found that some had begun production of two key components of the dopaminergic signaling system, tyrosine hydroxylase and the dopamine transporter protein. Other donor cells were found associated with tyrosine hydroxylase-positive host cells that had increased in size during seven months after the stem cell therapy was performed. These donor cells expressed markers characteristic of an astrocytic cell lineage, glial fibrillary protein and glia-derived neurotrophic factor.
The results suggest that the human neural stem cells differentiated after implantation, some forming dopaminergic neurons that may have directly mitigated the effects of the experimentally induced Parkinsonís disease and others forming glia that may have helped to sustain the still-viable cells of the hostís substantia nigra. Long-term primate studies are now needed to decide whether this stem cell therapy merits consideration for clinical application.
Message posted by: Keith Markey
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