Scientists at the D'OR Institute for Research and Education (IDOR) and Federal University of Rio de Janeiro (UFRJ) say they have taken what they describe as an important step toward using the implantation of stem cell-generated neurons as a treatment for Parkinson's disease. Using an FDA approved substance for treating stomach cancer, the team was able to grow dopamine-producing neurons derived from embryonic stem cells that remained healthy and functional for as long as 15 months after implantation into mice, restoring motor function without forming tumors.

Several studies have indicated that the transplantation of embryonic stem cells improves motor functions in animal models. However, until now, the procedure has shown to be unsafe, because of the risk of tumors upon transplantation. To address this issue, the researchers tested for the first time to pre-treat undifferentiated mouse embryonic stem cells with mitomycin C, a drug already prescribed to treat cancer. The substance blocks DNA replication and prevents the cells from multiplying out of control.

The researchers used 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 three and seven 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.

The scientists have also shown 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 the leader of the study Stevens Rehen, Ph.D., professor at UFRJ and researcher at IDOR.

The research (“Mitomycin-treated undifferentiated embryonic stem cells as a safe and effective therapeutic strategy in a mouse model of Parkinson's disease”) is reported in Frontiers in Cellular Neuroscience.

“Our findings indicate that treating mESCs [mouse embryonic stem cells] with mitomycin C prior to intrastriatal transplant is an effective strategy that could be further investigated as a novel alternative for treatment of Parkinson's disease,” wrote the investigators.








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