Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives

Go Itakura, Soya Kawabata, Miki Ando, Yuichiro Nishiyama, Keiko Sugai, Masahiro Ozaki, Tsuyoshi Iida, Toshiki Ookubo, Kota Kojima, Rei Kashiwagi, Kaori Yasutake, Hiromitsu Nakauchi, Hiroyuki Miyoshi, Narihito Nagoshi, Jun Kohyama, Akio Iwanami, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Human induced pluripotent stem cells (iPSCs) are promising in regenerative medicine. However, the risks of teratoma formation and the overgrowth of the transplanted cells continue to be major hurdles that must be overcome. Here, we examined the efficacy of the inducible caspase-9 (iCaspase9) gene as a fail-safe against undesired tumorigenic transformation of iPSC-derived somatic cells. We used a lentiviral vector to transduce iCaspase9 into two iPSC lines and assessed its efficacy in vitro and in vivo. In vitro, the iCaspase9 system induced apoptosis in approximately 95% of both iPSCs and iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs). To determine in vivo function, we transplanted iPSC-NS/PCs into the injured spinal cord of NOD/SCID mice. All transplanted cells whose mass effect was hindering motor function recovery were ablated upon transduction of iCaspase9. Our results suggest that the iCaspase9 system may serve as an important countermeasure against post-transplantation adverse events in stem cell transplant therapies.

Original languageEnglish
Pages (from-to)673-684
Number of pages12
JournalStem Cell Reports
Volume8
Issue number3
DOIs
Publication statusPublished - 2017 Mar 14

Fingerprint

Induced Pluripotent Stem Cells
Stem cells
Caspase 9
Transplantation
Derivatives
Stem Cells
Neoplastic Cell Transformation
Inbred NOD Mouse
Regenerative Medicine
SCID Mice
Neural Stem Cells
Teratoma
Recovery of Function
Cell- and Tissue-Based Therapy
Transplantation (surgical)
Transplants
Spinal Cord
Apoptosis
Cell Line
Genes

Keywords

  • iCaspase9
  • induced pluripotent stem cells (iPSCs)
  • iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs)
  • spinal cord injury

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives. / Itakura, Go; Kawabata, Soya; Ando, Miki; Nishiyama, Yuichiro; Sugai, Keiko; Ozaki, Masahiro; Iida, Tsuyoshi; Ookubo, Toshiki; Kojima, Kota; Kashiwagi, Rei; Yasutake, Kaori; Nakauchi, Hiromitsu; Miyoshi, Hiroyuki; Nagoshi, Narihito; Kohyama, Jun; Iwanami, Akio; Matsumoto, Morio; Nakamura, Masaya; Okano, Hideyuki.

In: Stem Cell Reports, Vol. 8, No. 3, 14.03.2017, p. 673-684.

Research output: Contribution to journalArticle

Itakura, G, Kawabata, S, Ando, M, Nishiyama, Y, Sugai, K, Ozaki, M, Iida, T, Ookubo, T, Kojima, K, Kashiwagi, R, Yasutake, K, Nakauchi, H, Miyoshi, H, Nagoshi, N, Kohyama, J, Iwanami, A, Matsumoto, M, Nakamura, M & Okano, H 2017, 'Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives', Stem Cell Reports, vol. 8, no. 3, pp. 673-684. https://doi.org/10.1016/j.stemcr.2017.02.003
Itakura, Go ; Kawabata, Soya ; Ando, Miki ; Nishiyama, Yuichiro ; Sugai, Keiko ; Ozaki, Masahiro ; Iida, Tsuyoshi ; Ookubo, Toshiki ; Kojima, Kota ; Kashiwagi, Rei ; Yasutake, Kaori ; Nakauchi, Hiromitsu ; Miyoshi, Hiroyuki ; Nagoshi, Narihito ; Kohyama, Jun ; Iwanami, Akio ; Matsumoto, Morio ; Nakamura, Masaya ; Okano, Hideyuki. / Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives. In: Stem Cell Reports. 2017 ; Vol. 8, No. 3. pp. 673-684.
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