Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model: Oncogenic transformation with epithelial-mesenchymal transition

Satoshi Nori, Yohei Okada, Soraya Nishimura, Takashi Sasaki, Go Itakura, Yoshiomi Kobayashi, Francois Renault-Mihara, Atsushi Shimizu, Ikuko Koya, Rei Yoshida, Jun Kudoh, Masato Koike, Yasuo Uchiyama, Eiji Ikeda, Yoshiaki Toyama, Masaya Nakamura, Hideyuki Okano

研究成果: Article査読

113 被引用数 (Scopus)

抄録

Previously, we described the safety and therapeutic potential of neurospheres (NSs) derived from a human induced pluripotent stem cell (iPSC) clone, 201B7, in a spinal cord injury (SCI) mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investigated another iPSC clone, 253G1, that we established by transducing OCT4, SOX2, and KLF4 into adult human dermal fibroblasts collected from the same donor who provided the 201B7 clone. The grafted 253G1-NSs survived, differentiated into three neural lineages, and promoted functional recovery accompanied by stimulated synapse formation 47 days after transplantation. However, long-term observation (for up to 103 days) revealed deteriorated motor function accompanied by tumor formation. The tumors consisted of Nestin+ undifferentiated neural cells and exhibited activation of the OCT4 transgene. Transcriptome analysis revealed that a heightened mesenchymal transition may have contributed to the progression of tumors derived from grafted cells.

本文言語English
ページ(範囲)360-373
ページ数14
ジャーナルStem cell reports
4
3
DOI
出版ステータスPublished - 2015 3 10

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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