Open AccessBrief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell‐Derived Teratomas
Author(s) -
Lee Andrew S.,
Tang Chad,
Hong Wan Xing,
Park Sujin,
BazalovaCarter Magdalena,
Nelson Geoff,
SanchezFreire Veronica,
Bakerman Isaac,
Zhang Wendy,
Neofytou Evgenios,
Connolly Andrew J.,
Chan Charles K.,
Graves Edward E.,
Weissman Irving L.,
Nguyen Patricia K.,
Wu Joseph C.
Publication year - 2017
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2653
Subject(s) - teratoma , embryonic stem cell , stem cell , biology , induced pluripotent stem cell , cancer research , radiobiology , radiation therapy , microbiology and biotechnology , pathology , medicine , genetics , gene
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 × 10 3 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. S tem C ells 2017;35:1994–2000