Selective Ablation of Tumorigenic Cells Following Human Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cell Transplantation in Spinal Cord Injury. (28th November 2018)

• Record Type: Journal Article
• Authors: Kojima, Kota; Miyoshi, Hiroyuki; Nagoshi, Narihito; Kohyama, Jun; Itakura, Go; Kawabata, Soya; Ozaki, Masahiro; Iida, Tsuyoshi; Sugai, Keiko; Ito, Shuhei; Fukuzawa, Ryuji; Yasutake, Kaori; Renault-Mihara, Francois; Shibata, Shinsuke; Matsumoto, Morio; Nakamura, Masaya; Okano, Hideyuki
• Is Part Of: Stem cells translational medicine. Volume 8:Number 3(2019)
• Page Start: 260
• Page End: 270
• Publication Date: 2018-11-28
• Subjects: Spinal cord injury -- Suicide gene -- Herpes simplex virus thymidine kinase -- Human induced pluripotent stem cell-derived neural stem/progenitor cell -- Stem cell therapy; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.18-0096
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: 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 : Abstract : The herpes simplex virus thymidine kinase (HSVtk) gene was introduced into a tumorigenic cell line of human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) prior to transplantation into spinal cord injury mouse models. Administration of ganciclovir (GCV) following transplantation successfully ablated the immature tumorigenic cells while preserving the mature neuronal cells and the improved motor function.