Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases

Keiko Sugai, Ryuji Fukuzawa, Tomoko Shofuda, Hayato Fukusumi, Soya Kawabata, Yuichiro Nishiyama, Yuichiro Higuchi, Kenji Kawai, Miho Isoda, Daisuke Kanematsu, Tomoko Hashimoto-Tamaoki, Jun Kohyama, Akio Iwanami, Hiroshi Suemizu, Eiji Ikeda, Morio Matsumoto, Yonehiro Kanemura, Masaya Nakamura, Hideyuki Okano

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The risk of tumorigenicity is a hurdle for regenerative medicine using induced pluripotent stem cells (iPSCs). Although teratoma formation is readily distinguishable, the malignant transformation of iPSC derivatives has not been clearly defined due to insufficient analysis of histology and phenotype. In the present study, we evaluated the histology of neural stem/progenitor cells (NSPCs) generated from integration-free human peripheral blood mononuclear cell (PBMC)-derived iPSCs (iPSC-NSPCs) following transplantation into central nervous system (CNS) of immunodeficient mice. We found that transplanted iPSC-NSPCs produced differentiation patterns resembling those in embryonic CNS development, and that the microenvironment of the final site of migration affected their maturational stage. Genomic instability of iPSCs correlated with increased proliferation of transplants, although no carcinogenesis was evident. The histological classifications presented here may provide cues for addressing potential safety issues confronting regenerative medicine involving iPSCs.

Original languageEnglish
Article number85
JournalMolecular brain
Volume9
Issue number1
DOIs
Publication statusPublished - 2016 Sep 19

Keywords

  • Carcinogenesis
  • Cell transplantation
  • Human induced pluripotent stem cells
  • Pathology
  • Regenerative medicine

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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    Sugai, K., Fukuzawa, R., Shofuda, T., Fukusumi, H., Kawabata, S., Nishiyama, Y., Higuchi, Y., Kawai, K., Isoda, M., Kanematsu, D., Hashimoto-Tamaoki, T., Kohyama, J., Iwanami, A., Suemizu, H., Ikeda, E., Matsumoto, M., Kanemura, Y., Nakamura, M., & Okano, H. (2016). Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases. Molecular brain, 9(1), [85]. https://doi.org/10.1186/s13041-016-0265-8