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Mol Brain. 2016 Sep 19;9(1):85. doi: 10.1186/s13041-016-0265-8.

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

Author information

1
Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, 160-8582, Japan.
2
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan.
3
Department of Pathology, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, 183-8561, Japan.
4
Division of Stem Cell Research, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka, 540-0006, Japan.
5
Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka, 540-0006, Japan.
6
Central Institute for Experimental Animals, Kawasaki, Kanagawa, 210-0821, Japan.
7
Regenerative & Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd., Kobe, Hyogo, 650-0047, Japan.
8
Department of Genetics, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan.
9
Department of Pathology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
10
Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka, 540-0006, Japan.
11
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan. hidokano@a2.keio.jp.

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.

KEYWORDS:

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

PMID:
27642008
PMCID:
PMC5027634
DOI:
10.1186/s13041-016-0265-8
[Indexed for MEDLINE]
Free PMC Article

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