External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas. Stem cells (Dayton, Ohio) Lee, A. S., Tang, C., Hong, W. X., Park, S., Bazalova, M., Nelson, G., Sanchez-Freire, V., Bakerman, I., Zhang, W., Neofytou, E., Connolly, A. J., Chan, C. K., Graves, E. E., Weissman, I. L., Nguyen, P. K., Wu, J. C. 2017

Abstract

Human pluripotent stem cells (hPSCs), including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), have great potential as an unlimited donor source for cell-based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth. We present the evidence that EBRT is effective in arresting growth of hESC-derived teratomas in vivo at day 28 post-implantation by utilizing a microCT irradiator capable of targeted treatment in small animals. Within several days of irradiation, teratomas derived from injection of undifferentiated hESCs and hiPSCs demonstrated complete growth arrest lasting several months. In addition, EBRT reduced re-seeding potential of teratoma cells during serial transplantation experiments, requiring irradiated teratomas to be seeded at 1x10(3) higher doses to form new teratomas. We demonstrate that radiation induces teratoma cell apoptosis, senescence, and growth arrest, similar to established radiobiology mechanisms. Taken together, these results provide proof of concept for the use of EBRT in the treatment of existing teratomas and highlight a strategy to increase the safety of stem cell-based therapies. This article is protected by copyright. All rights reserved.

View details for PubMedID 28600830