Pathological Classification of Human IPSC-derived Neural Stem/progenitor Cells Towards Safety Assessment of Transplantation Therapy for CNS Diseases

Overview

Journal Mol Brain

Publisher Biomed Central

Specialties Molecular Biology
Neurology

Date 2016 Sep 20

PMID 27642008

Citations 30

Authors

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

Affiliations

Soon will be listed here.

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.

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