Selective Ablation of Tumorigenic Cells Following Human Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cell Transplantation in Spinal Cord Injury
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- Kota Kojima
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
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- Hiroyuki Miyoshi
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
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- Narihito Nagoshi
- b Department of Orthopaedic Surgery Keio University School of Medicine, Tokyo, Japan
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- Jun Kohyama
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
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- Go Itakura
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
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- Soya Kawabata
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
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- Masahiro Ozaki
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
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- Tsuyoshi Iida
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
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- Keiko Sugai
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
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- Shuhei Ito
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
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- Ryuji Fukuzawa
- c Department of Pathology International University of Health and Welfare, Chiba, Japan
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- Kaori Yasutake
- b Department of Orthopaedic Surgery Keio University School of Medicine, Tokyo, Japan
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- Francois Renault-Mihara
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
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- Shinsuke Shibata
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
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- Morio Matsumoto
- b Department of Orthopaedic Surgery Keio University School of Medicine, Tokyo, Japan
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- Masaya Nakamura
- b Department of Orthopaedic Surgery Keio University School of Medicine, Tokyo, Japan
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- Hideyuki Okano
- a Department of Physiology Keio University School of Medicine, Tokyo, Japan
説明
<jats:title>Abstract</jats:title><jats:p>Tumorigenesis is an important problem that needs to be addressed in the field of human stem/progenitor cell transplantation for the treatment of subacute spinal cord injury (SCI). When certain “tumorigenic” cell lines are transplanted into the spinal cord of SCI mice model, there is initial improvement of motor function, followed by abrupt deterioration secondary to the effect of tumor growth. A significant proportion of the transplanted cells remains undifferentiated after transplantation and is thought to increase the risk of tumorigenesis. In this study, using lentiviral vectors, we introduced the herpes simplex virus type 1 thymidine kinase (HSVtk) gene into a human induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC) line that is known to undergo tumorigenic transformation. Such approach enables selective ablation of the immature proliferating cells and thereby prevents subsequent tumor formation. In vitro, the HSVtk system successfully ablated the immature proliferative neural cells while preserving mature postmitotic neuronal cells. Similar results were observed in vivo following transplantation into the injured spinal cords of immune-deficient (nonobese diabetic–severe combined immune-deficient) mice. Ablation of the proliferating cells exerted a protective effect on the motor function which was regained after transplantation, simultaneously defending the spinal cord from the harmful tumor growth. These results suggest a potentially promising role of suicide genes in opposing tumorigenesis during stem cell therapy. This system allows both preventing and treating tumorigenesis following hiPSC-NS/PC transplantation without sacrificing the improved motor function. Stem Cells Translational Medicine 2019;8:260&270</jats:p><jats:sec><jats:title/></jats:sec>
収録刊行物
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- Stem Cells Translational Medicine
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Stem Cells Translational Medicine 8 (3), 260-270, 2018-11-28
Oxford University Press (OUP)
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詳細情報 詳細情報について
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- CRID
- 1360567180249538048
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- ISSN
- 21576580
- 21576564
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- データソース種別
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- Crossref
- KAKEN