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

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

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 journal › Article › peer-review

37 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 language	English
Article number	85
Journal	Molecular brain
Volume	9
Issue number	1
DOIs	https://doi.org/10.1186/s13041-016-0265-8
Publication status	Published - 19-09-2016
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Biology
Cellular and Molecular Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/s13041-016-0265-8

Cite this

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), Article 85. https://doi.org/10.1186/s13041-016-0265-8

@article{db64b9f4c6634bb089a384e6795717b0,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

month = sep,

day = "19",

doi = "10.1186/s13041-016-0265-8",

language = "English",

volume = "9",

journal = "Molecular brain",

issn = "1756-6606",

publisher = "BioMed Central",

number = "1",

}

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, vol. 9, no. 1, 85. https://doi.org/10.1186/s13041-016-0265-8

TY - JOUR

T1 - Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases

AU - Sugai, Keiko

AU - Fukuzawa, Ryuji

AU - Shofuda, Tomoko

AU - Fukusumi, Hayato

AU - Kawabata, Soya

AU - Nishiyama, Yuichiro

AU - Higuchi, Yuichiro

AU - Kawai, Kenji

AU - Isoda, Miho

AU - Kanematsu, Daisuke

AU - Hashimoto-Tamaoki, Tomoko

AU - Kohyama, Jun

AU - Iwanami, Akio

AU - Suemizu, Hiroshi

AU - Ikeda, Eiji

AU - Matsumoto, Morio

AU - Kanemura, Yonehiro

AU - Nakamura, Masaya

AU - Okano, Hideyuki

PY - 2016/9/19

Y1 - 2016/9/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84988420033&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84988420033&partnerID=8YFLogxK

U2 - 10.1186/s13041-016-0265-8

DO - 10.1186/s13041-016-0265-8

M3 - Article

C2 - 27642008

AN - SCOPUS:84988420033

SN - 1756-6606

VL - 9

JO - Molecular brain

JF - Molecular brain

IS - 1

M1 - 85

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this