Radiation therapy reduces risk of tumors in stem cell-based neurosurgery
In stem cell therapy for Parkinson's disease, an important risk factor is the emergence of tumors. Immature progenitors formed by the stem cells have an unacceptably high proliferation rate. It is therefore essential to identify these cells and either remove them from the transplant or suppress their proliferation capacity. Professor Jun Takahashi believes that cell sorting is adequate, but an auxiliary method should also be considered, saying that, "We have never observed tumor formation using our cell sorting protocol, but we want a fail-safe therapy." In the latest publication from his lab, researchers show that gamma-ray irradiation is an effective fail-safe therapy that removes from the graft progenitor cells that could cause tumors.
A graft actually consists of many types of proliferating cells, but it is those that make up neural rosettes that cause the greatest concern. "Neural rosettes are the main contributors to tumor formation," said Takahashi. On the other hand, other proliferative cells will go on to make mature neurons, which will replace those lost by Parkinson's disease. The study shows that the cells constituting neural rosettes are distinguishable by their expression of two protein markers, SOX1 and PAX6. It also found that the rosettes emerged by 4 weeks after transplantation in rats, but vanished by 14 weeks, giving the scientists a clear time window to conduct the irradiation therapy. Whole-brain radiation treatment on rats at 4 weeks after the transplant inhibited the proliferation of the SOX1+PAX6+ cells in the graft, but did not affect those that would become mature neurons. "We think it is partly due to a slow proliferation rate" of the other progenitor cells, explained Takahashi.
Takahashi is excited about the implications of this fail-safe therapy for the first iPS cell-based neurosurgery. "We hope to start in the next couple of years," he said.
Journal: Stem Cells and Development
Title: Fail-safe therapy by gamma-ray irradiation against tumor formation by human induced pluripotent stem cell-dervied neural progenitors
Authors: Mitsuko Katsukawa (1), Yusuke Nakajima (1), Akiko Fukumoto (1), Daisuke Doi (1), Jun Takahashi (1,2,3)
- Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
- Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto Japan
- Kyoto University Graduate School of Medicine