Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration

Michiko Mandai; Akira Watanabe; Yasuo Kurimoto; Yasuhiko Hirami; Chikako Morinaga; Takashi Daimon; Masashi Fujihara; Hiroshi Akimaru; Noriko Sakai; Yumiko Shibata; Motoki Terada; Yui Nomiya; Shigeki Tanishima; Masahiro Nakamura; Hiroyuki Kamao; Sunao Sugita; Akishi Onishi; Tomoko Ito; Kanako Fujita; Shin Kawamata; Masahiro J Go; Chikara Shinohara; Ken-Ichiro Hata; Masanori Sawada; Midori Yamamoto; Sachiko Ohta; Yasuo Ohara; Kenichi Yoshida; Junko Kuwahara; Yuko Kitano; Naoki Amano; Masafumi Umekage; Fumiyo Kitaoka; Azusa Tanaka; Chihiro Okada; Naoko Takasu; Seishi Ogawa; Shinya Yamanaka; Masayo Takahashi

doi:10.1056/NEJMoa1608368

Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration

N Engl J Med. 2017 Mar 16;376(11):1038-1046. doi: 10.1056/NEJMoa1608368.

Authors

Michiko Mandai¹, Akira Watanabe¹, Yasuo Kurimoto¹, Yasuhiko Hirami¹, Chikako Morinaga¹, Takashi Daimon¹, Masashi Fujihara¹, Hiroshi Akimaru¹, Noriko Sakai¹, Yumiko Shibata¹, Motoki Terada¹, Yui Nomiya¹, Shigeki Tanishima¹, Masahiro Nakamura¹, Hiroyuki Kamao¹, Sunao Sugita¹, Akishi Onishi¹, Tomoko Ito¹, Kanako Fujita¹, Shin Kawamata¹, Masahiro J Go¹, Chikara Shinohara¹, Ken-Ichiro Hata¹, Masanori Sawada¹, Midori Yamamoto¹, Sachiko Ohta¹, Yasuo Ohara¹, Kenichi Yoshida¹, Junko Kuwahara¹, Yuko Kitano¹, Naoki Amano¹, Masafumi Umekage¹, Fumiyo Kitaoka¹, Azusa Tanaka¹, Chihiro Okada¹, Naoko Takasu¹, Seishi Ogawa¹, Shinya Yamanaka¹, Masayo Takahashi¹

Affiliation

¹ From the Division of Ophthalmology, Institute of Biomedical Research and Innovation Hospital, Foundation for Biomedical Research and Innovation (M.M., Y. Kurimoto, Y.H., M.F., M.Y., S. Ohta, M. Takahashi), Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology (M.M., C.M., H.A., N.S., Y.S., M. Terada, H.K., S.S., A.O., M.Y., M. Takahashi), the Department of Ophthalmology, Kobe City Medical Center General Hospital (Y.Kurimoto, Y.H., M.F.), the Department of Clinical Trial Management, Institute of Biomedical Research and Innovation Hospital, Foundation for Biomedical Research and Innovation (T.I., K.F.), and Research and Development Center for Cell Therapy, Foundation for Biomedical Research and Innovation (S.K., M.J.G.), Kobe, Center for iPS Cell Research and Application (CiRA) (A.W., Y.N., M.N., J.K., Y. Kitano, N.A., M.U., F.K., A.T., N.T., S.Y.), Institute for Integrated Cell-Material Sciences (iCeMS) (A.W.), and Department of Pathology and Tumor Biology, Graduate School of Medicine (K.Y., S. Ogawa), Kyoto University, Kyoto, the Department of Biostatistics, Hyogo College of Medicine, Nishinomiya (T.D.), Platform of Therapeutics for Rare Disease, National Institutes of Biomedical Innovation, Health, and Nutrition, Ibaraki (H.A.), Mitsubishi Space Software, Tokyo (S.T., Y.O., C.O.), the Department of Ophthalmology, Kawasaki Medical School, Kurashiki (H.K.), Japan Tissue Engineering, Gamagori (C.S., K.H.), and HEALIOS K.K., Tokyo (M.S.) - all in Japan; and Gladstone Institute of Cardiovascular Disease, San Francisco (S.Y.).

PMID: 28296613
DOI: 10.1056/NEJMoa1608368

Abstract

We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Cell Culture Techniques
Cell Differentiation
Feasibility Studies
Female
Fibroblasts
Humans
Induced Pluripotent Stem Cells / cytology*
Macular Degeneration / therapy*
Male
Retinal Pigment Epithelium / cytology*
Retinal Pigment Epithelium / transplantation
Transplantation, Autologous