Researchers have taken a step toward using the implantation of stem cell-generated neurons as a treatment for Parkinson's disease.
Parkinson's, which affect as many 10 million people in the world, is linked to a depletion of dopamine-producing neurons in the brain. Current treatments include medications and electrical implants in the brain which cause severe adverse effects over time and fail to prevent disease progression. Several studies have indicated that the transplantation of embryonic stem cells improves motor functions in animal models but the procedure has shown to be unsafe, because of the risk of tumors upon transplantation.
Until now. Using an FDA approved drug for treating stomach cancer, mitomycin C, they were able to pre-treat undifferentiated mouse embryonic stem cells and grow dopamine-producing neurons that remained healthy and functional for as long as 15 months after implantation into mice, restoring motor function without forming tumors in mice modeled for Parkinson's.
The animals were separated in three groups. The first one, the control group, did not receive the stem cell implant. The second one, received the implant of stem cells which were not treated with mitomycin C and the third one received the mitomycin C treated cells.
After the injection of 50,000 untreated stem cells, the animals of the second group showed improvement in motor functions but all of them died between 3 and 7 weeks later. These animals also developed intracerebral tumors. In contrast, animals receiving the treated stem cells showed improvement of Parkinson's symptoms and survived until the end of the observation period of 12 weeks post-transplant with no tumors detected. Four of these mice were monitored for as long as 15 months with no signs of pathology.
They also found that treating the stem cells with mitomycin C induced a four-fold increase in the release of dopamine after in vitro differentiation.
"This simple strategy of shortly exposing pluripotent stem cells to an anti-cancer drug turned the transplant safer, by eliminating the risk of tumor formation," says study leader Stevens Rehen, Professor at Federal University of Rio de Janeiro and researcher at D'OR Institute for Research and Education.
The authors are working toward a clinical trial using pluripotent stem cells treated with mitomycin C prior to transplant to treat Parkinson's patients and also other neurodegenerative conditions.
Citation: Details: M. Acquarone, T. Melo, F. G. Meireles Ferreira, J. Brito-Moreira, G. Oliveira, S. Ferreira, N. Castro, F. Tovar-Moll, J. C. Houzel, S. K. Rehen. Mitomycin-treated undifferentiated embryonic stem cells as a safe and effective therapeutic strategy in a mouse model of Parkinson's disease. Frontiers in Cellular Neuroscience.
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