Dataset Information

Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas.

ABSTRACT: Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (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 evidence that EBRT is effective in arresting growth of hESC-derived teratomas in vivo at day 28 post-implantation by using 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 reseeding potential of teratoma cells during serial transplantation experiments, requiring irradiated teratomas to be seeded at 1 × 103 higher doses to form new teratomas. We demonstrate that irradiation 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. Stem Cells 2017;35:1994-2000.

SUBMITTER: Lee AS

PROVIDER: S-EPMC5568072 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas.

Lee Andrew S AS Tang Chad C Hong Wan Xing WX Park Sujin S Bazalova-Carter Magdalena M Nelson Geoff G Sanchez-Freire Veronica V Bakerman Isaac I Zhang Wendy W Neofytou Evgenios E Connolly Andrew J AJ Chan Charles K CK Graves Edward E EE Weissman Irving L IL Nguyen Patricia K PK Wu Joseph C JC

Stem cells (Dayton, Ohio) 20170710 8

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (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 evidence that EBRT is eff ...[more]

PMID: 28600830

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Project description:PurposeBeam angle optimization is a critical issue for modern radiotherapy (RT) and is a challenging task, especially for large body sizes and noncoplanar designs. Noncoplanar RT techniques may have dosimetric advantages but increase the risk of mechanical collision. We propose a software solution to accurately predict colliding/noncolliding configurations for coplanar and noncoplanar beams.Materials and methodsIndividualized software models for two different linear accelerators were built to simulate noncolliding gantry orientations for phantom/patient subjects. The sizes and shapes of the accelerators were delineated based on their manuals and on-site measurements. The external surfaces of the subjects were automatically contoured based on computed tomography (CT) simulations. An Alderson Radiation Therapy phantom was used to predict the accuracy of spatial collision prediction by the software. A gantry collision problem encountered by one patient during initial setup was also used to test the validity of the software. Results: In the comparison between the software estimates and on-site measurements, the noncoplanar collision angles were all predicted within a 5-degree difference in gantry position. The confusion matrix was calculated for each of the two empty accelerator models, and the accuracies were 98.7% and 97.3%. The true positive rates were 97.7% and 96.9%, while the true negative rates were 99.8% and 97.9%, respectively. For the phantom study, the collision angles were predicted within a 5-degree difference. The software successfully predicted the collision problem encountered by the breast cancer patient in the initial setup position and generated shifted coordinates that were validated to correspond to a noncolliding geometry.ConclusionThe developed software effectively and accurately predicted collisions for accelerator-only, phantom, and patient setups. This software may help prevent collisions and expand the range of spatially applicable beam angles.

Dataset Information

Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas.

Publications

Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas.

Similar Datasets

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