Steps toward safe cell therapy using induced pluripotent stem cells.
The enthusiasm for producing patient-specific human embryonic stem cells using somatic nuclear transfer has somewhat abated in recent years because of ethical, technical, and political concerns. However, the interest in generating induced pluripotent stem cells (iPSCs), in which pluripotency can be obtained by transcription factor transduction of various somatic cells, has rapidly increased. Human iPSCs are anticipated to open enormous opportunities in the biomedical sciences in terms of cell therapies for regenerative medicine and stem cell modeling of human disease. On the other hand, recent reports have emphasized the pitfalls of iPSC technology, including the potential for genetic and epigenetic abnormalities, tumorigenicity, and immunogenicity of transplanted cells. These constitute serious safety-related concerns for iPSC-based cell therapy. However, preclinical data supporting the safety and efficacy of iPSCs are also accumulating. In this Review, recent achievements and future tasks for safe iPSC-based cell therapy are summarized, using regenerative medicine for repair strategies in the damaged central nervous system (CNS) as a model. Insights on safety and preclinical use of iPSCs in cardiovascular repair model are also discussed.
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. hidokano@a2.keio.jp
Hideyuki
H
Okano
Masaya
M
Nakamura
Kenji
K
Yoshida
Yohei
Y
Okada
Osahiko
O
Tsuji
Satoshi
S
Nori
Eiji
E
Ikeda
Shinya
S
Yamanaka
Kyoko
K
Miura
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D065150:Cellular Reprogramming; D018507:Gene Expression Regulation, Developmental; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D044968:Regenerative Medicine / Q000379:methods*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
D014157:Transcription Factors