AsianScientist (Nov. 7, 2014) – In a study published in the Proceedings of the National Academy of Science, scientists have shown that stem cells transplanted into the brains of rats are able to release dopamine. This achievement represents an important proof-of-concept for the treatment of Parkinson’s disease, paving the way for clinical trials in humans.
With their ability to differentiate into any cell of the body, it has been hoped that stem cells would transform regenerative medicine, yielding treatments for conditions such as diabetes and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. However, it has proven difficult to direct the differentiation of stem cells into the types of cells they are intended to replace.
In Parkinson’s disease, the loss of neurons with the ability to secrete the neurotransmitter dopamine leads to progressively deteriorating motor control and brain function. Previous studies have shown that transplanting primitive neural stem cells (pNSCs) into the brains of rats with symptoms of Parkinson’s disease is able to alleviate the condition.
However, before the procedure can be tested in humans, two crucial questions remain to be answered: whether the transplanted cells are able to increase dopamine production in vivo, and if the dopamine is produced, whether it is by the newly grafted cells or resident cells “repaired” by the transplant.
To answer these questions, a research group led by Professor Zhou Zhuan from Peking University combined two techniques to show that differentiated pNSCs cells were indeed able to produce dopamine in both brain slices and in vivo.
Firstly, pNSCs were derived from human embryonic stem cells and further differentiated into dopamine-like neurons (DAns) by treatment with SHH and FGF8. Transplantation of the pNSC-DAns cells into the brains of a rat model of Parkinson’s disease was able to reduce sideways rotation caused by the drug apomorphine.
In both brain slices and live mice, microdialysis high-performance liquid chromatography (HPLC) showed that the transplanted pNSC-DAns cells were able to rescue the production of dopamine. However, while microdialysis HPLC was able to unequivocally show that dopamine was indeed produced, it was not able to show that the transplanted cells were producing the dopamine rather than existing brain cells that were stimulated by the procedure.
To address this issue, the authors used carbon fiber electrodes to measure the electrical signals caused by the release of dopamine. Called CFE amperometry, this technique allowed the researchers to measure changes at the micrometer scale at millisecond timeframes, providing high spatiotemporal resolution data. The CFE amperometry measurements showed that transplanted pNSC-DAns cells were able to rescue the response to high potassium levels by 29 percent in vivo.
The ability of stem cell-derived neurons to successfully engraft and begin producing dopamine demonstrated in this study offers hope for patients suffering from Parkinson’s disease. The authors note that the method used to obtain pNSC-DAns could also be used on induced pluripotent stem cells, opening opportunities to generate patient-specific dopamine producing cells.
The article can be found at: Kang et al. (2014) Dopamine Release from Transplanted Neural Stem Cells in Parkinsonian Rat Striatum in vivo.
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Copyright: Asian Scientist Magazine; Photo: Joseph Elsbernd/Flickr/CC.
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