Brazilian researchers at D’OR Institute for Research and Education (IDOR) and Federal University of Rio de Janeiro (UFRJ) 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, Rehen and colleagues were 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 tumours.
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 tumours upon transplantation.
To address this issue, the researchers tested undifferentiated mouse embryonic stem cells pre-treated with mitomycin C, a drug already prescribed to treat cancer. The substance blocks DNA replication and prevents cells from multiplying out of control.
The researchers used mice modeled for Parkinson’s. The animals were separated into 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 tumours. 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 tumours detected. Four of these mice were monitored for as long as 15 months with no signs of pathology.
Furthermore, 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.
Journal Reference:
Mariana Acquarone, Thiago Melo, Fernanda G. Meireles Ferreira, Jordano Brito-Moreira, Gabriel Oliveira, Sergio Ferreira, Newton Castro, Fernanda Tovar-Moll, Jean Christophe Houzel and Stevens K. Rehen. Mitomycin-treated undifferentiated embryonic stem cells as a safe and effective therapeutic strategy in a mouse model of Parkinson’s disease. Front. Cell. Neurosci., 2015 DOI: 10.3389/fncel.2015.00097