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自体诱导干细胞来源的视网膜细胞用于治疗黄斑变性
Autologous Induced Stem-Cell–Derived Retinal Cells for Macular Degeneration


Michiko Mandai ... 其他 • 2017.03.16
相关阅读
• 重振再生医学的监管 • 读懂衰老 • 澄清干细胞疗法的获益与风险 • 干细胞临床应用中的两个极端

再生医学领域的里程碑:诱导多能干细胞治疗黄斑变性

 

金子兵†*,魏来‡*

† 温州医科大学附属眼视光医院;温州医科大学干细胞研究所;省部共建眼视光学与视觉科学国家重点实验室; ‡ 中山大学中山眼科中心;眼科学国家重点实验室

* 通讯作者

 

老年性黄斑变性(AMD,又称年龄相关性黄斑变性)是不可逆失明的最主要病因之一。随着包括中国在内的许多国家的人口老龄化高峰逼近,该病将成为国家和社会发展的重大负担。目前的临床治疗仍然停留在“对症治疗”甚至“无药可治”的阶段,因而干细胞干预治疗黄斑变性是国内外普遍认同的最有前景的全新治疗方向1。然而,如何突破干细胞治疗的“医学伦理限制”“免疫排斥难题”,同时兼顾“治疗安全性和有效性问题”,是一直以来的挑战性难题。在本期《新英格兰医学杂志》发表的一篇文章2中,作者利用AMD患者自体诱导多能干细胞(iPSC)分化诱导而来的视网膜色素上皮(RPE)细胞移植片,经视网膜下腔手术移植途径治疗黄斑变性,成功验证了iPSC治疗黄斑变性患者的可行性和安全性,开创了再生医学领域iPSC临床转化的先河,为再生医学领域敲开了第一扇门,其意义十分重大。

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概述


我们评估了将诱导多能干细胞(iPSC)分化产生的单层视网膜色素上皮(RPE)细胞移植到一例新生血管性老年性黄斑变性患者眼内的可行性。2例晚期新生血管性老年性黄斑变性患者的皮肤成纤维细胞被用于生成iPSC,并进而分化成RPE细胞。我们对iPSC及其产生的RPE细胞进行了广泛的测试。对其中1例患者进行了包括视网膜下新生血管膜切除及自体来源iPSC生成RPE细胞移植的手术。术后1年移植片依然完整,最佳矫正视力没有改善或恶化,并且存在囊样黄斑水肿(由实现再生医学高速公路计划[Highway Program for Realization of Regenerative Medicine]等资助;大学医院医学信息网络临床试验注册[University Hospital Medical Information Network Clinical Trials Registry,UMIN-CTR]号为UMIN000011929)。





作者信息

Michiko Mandai, M.D., Ph.D., Akira Watanabe, Ph.D., Yasuo Kurimoto, M.D., Ph.D., Yasuhiko Hirami, M.D., Ph.D., Chikako Morinaga, Ph.D., Takashi Daimon, Ph.D., Masashi Fujihara, M.D., Ph.D., Hiroshi Akimaru, Ph.D., Noriko Sakai, B.S., Yumiko Shibata, M.S., Motoki Terada, Yui Nomiya, M.S., Shigeki Tanishima, B.S., Masahiro Nakamura, M.D., Ph.D., Hiroyuki Kamao, M.D., Ph.D., Sunao Sugita, M.D., Ph.D., Akishi Onishi, Ph.D., Tomoko Ito, Kanako Fujita, Shin Kawamata, M.D., Ph.D., Masahiro J. Go, Ph.D., Chikara Shinohara, Ph.D., Ken-ichiro Hata, D.D.S., Ph.D., Masanori Sawada, M.D., Ph.D., Midori Yamamoto, Sachiko Ohta, Yasuo Ohara, B.S., Kenichi Yoshida, M.D., Ph.D., Junko Kuwahara, Yuko Kitano, M.S., Naoki Amano, M.S., Masafumi Umekage, M.S., Fumiyo Kitaoka, Ph.D., Azusa Tanaka, Ph.D., Chihiro Okada, M.S., Naoko Takasu, M.S., Seishi Ogawa, M.D., Ph.D., Shinya Yamanaka, M.D., Ph.D., and Masayo Takahashi, M.D., Ph.D.
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.). Address reprint requests to Dr. Takahashi at the Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan, or at retinalab@cdb.riken.jp; or to Dr. Yamanaka at the Center for iPS Cell Research and Application, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan, or at yamanaka@cira.kyoto-u.ac.jp.

 

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