RRC ID 37539
著者 Katsukawa M, Nakajima Y, Fukumoto A, Doi D, Takahashi J.
タイトル Fail-Safe Therapy by Gamma-Ray Irradiation Against Tumor Formation by Human-Induced Pluripotent Stem Cell-Derived Neural Progenitors.
ジャーナル Stem Cells Dev
Abstract Cell replacement therapy holds great promise for Parkinson's disease (PD), but residual undifferentiated cells and immature neural progenitors in the therapy may cause tumor formation. Although cell sorting could effectively exclude these proliferative cells, from the viewpoint of clinical application, there exists no adequate coping strategy in the case of their contamination. In this study, we analyzed a component of proliferative cells in the grafts of human-induced pluripotent stem cell-derived neural progenitors and investigated the effect of radiation therapy on tumor formation. In our differentiating protocol, analyses of neural progenitors (day 19) revealed that the proliferating cells expressed early neural markers (SOX1, PAX6) or a dopaminergic neuron progenitor marker (FOXA2). When grafted into the rat striatum, these immature neurons gradually became postmitotic in the brain, and the rosette structures disappeared at 14 weeks. However, at 4-8 weeks, the SOX1(+)PAX6(+) cells formed rosette structures in the grafts, suggesting their tumorigenic potential. Therefore, to develop a fail-safe therapy against tumor formation, we investigated the effect of radiation therapy. At 4 weeks posttransplantation, when KI67(+) cells comprised the highest ratio, radiation therapy with (137)Cs Gammacell Exactor for tumor-bearing immunodeficient rats showed a significant decrease in graft volume and percentage of SOX1(+)KI67(+) cells in the graft, thus demonstrating the preventive effect of gamma-ray irradiation against tumorigenicity. These results give us critical criteria for the safety of future cell replacement therapy for PD.
巻・号 25(11)
ページ 815-25
公開日 2016-6-1
DOI 10.1089/scd.2015.0394
PMID 27059007
MeSH Carcinogenesis / pathology* Carcinogenesis / radiation effects* Cell Differentiation / radiation effects Cell Line Cell Proliferation / radiation effects Dopaminergic Neurons / cytology Dopaminergic Neurons / radiation effects Gamma Rays* Humans Immunohistochemistry Induced Pluripotent Stem Cells / pathology* Induced Pluripotent Stem Cells / radiation effects Mesencephalon / cytology Neural Stem Cells / pathology* Neural Stem Cells / radiation effects Spheroids, Cellular / cytology Spheroids, Cellular / radiation effects Stem Cell Transplantation
IF 3.153
引用数 20
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL TRANSPLANTATION CELL & TISSUE ENGINEERING HEMATOLOGY
リソース情報
ラット F344-Il2rgem2Kyo (strainID=979)