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Induced Fetal Human Muscle Stem Cells with High Therapeutic Potential in a Mouse Muscular Dystrophy Model.
Stem Cell Reports. 2020 07 14; 15(1):80-94.SC

Abstract

Duchenne muscular dystrophy (DMD) is a progressive and fatal muscle-wasting disease caused by DYSTROPHIN deficiency. Cell therapy using muscle stem cells (MuSCs) is a potential cure. Here, we report a differentiation method to generate fetal MuSCs from human induced pluripotent stem cells (iPSCs) by monitoring MYF5 expression. Gene expression profiling indicated that MYF5-positive cells in the late stage of differentiation have fetal MuSC characteristics, while MYF5-positive cells in the early stage of differentiation have early myogenic progenitor characteristics. Moreover, late-stage MYF5-positive cells demonstrated good muscle regeneration potential and produced DYSTROPHIN in vivo after transplantation into DMD model mice, resulting in muscle function recovery. The engrafted cells also generated PAX7-positive MuSC-like cells under the basal lamina of DYSTROPHIN-positive fibers. These findings suggest that MYF5-positive fetal MuSCs induced in the late stage of iPSC differentiation have cell therapy potential for DMD.

Authors+Show Affiliations

Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: zhaoming@cira.kyoto-u.ac.jp.Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Asahi Kasei Co., Ltd., 1-105 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo, Japan.Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Asahi Kasei Co., Ltd., 1-105 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo, Japan.Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.Faculty of Rehabilitation Science, Nagoya Gakuin University, 1350 Kamishinano-cho, Seto City, Aichi 480-1298, Japan.Department of Anatomy, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: hsakurai@cira.kyoto-u.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32619494

Citation

Zhao, Mingming, et al. "Induced Fetal Human Muscle Stem Cells With High Therapeutic Potential in a Mouse Muscular Dystrophy Model." Stem Cell Reports, vol. 15, no. 1, 2020, pp. 80-94.
Zhao M, Tazumi A, Takayama S, et al. Induced Fetal Human Muscle Stem Cells with High Therapeutic Potential in a Mouse Muscular Dystrophy Model. Stem Cell Reports. 2020;15(1):80-94.
Zhao, M., Tazumi, A., Takayama, S., Takenaka-Ninagawa, N., Nalbandian, M., Nagai, M., Nakamura, Y., Nakasa, M., Watanabe, A., Ikeya, M., Hotta, A., Ito, Y., Sato, T., & Sakurai, H. (2020). Induced Fetal Human Muscle Stem Cells with High Therapeutic Potential in a Mouse Muscular Dystrophy Model. Stem Cell Reports, 15(1), 80-94. https://doi.org/10.1016/j.stemcr.2020.06.004
Zhao M, et al. Induced Fetal Human Muscle Stem Cells With High Therapeutic Potential in a Mouse Muscular Dystrophy Model. Stem Cell Reports. 2020 07 14;15(1):80-94. PubMed PMID: 32619494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induced Fetal Human Muscle Stem Cells with High Therapeutic Potential in a Mouse Muscular Dystrophy Model. AU - Zhao,Mingming, AU - Tazumi,Atsutoshi, AU - Takayama,Satoru, AU - Takenaka-Ninagawa,Nana, AU - Nalbandian,Minas, AU - Nagai,Miki, AU - Nakamura,Yumi, AU - Nakasa,Masanori, AU - Watanabe,Akira, AU - Ikeya,Makoto, AU - Hotta,Akitsu, AU - Ito,Yuta, AU - Sato,Takahiko, AU - Sakurai,Hidetoshi, Y1 - 2020/07/02/ PY - 2019/06/24/received PY - 2020/06/03/revised PY - 2020/06/03/accepted PY - 2020/7/4/pubmed PY - 2020/7/4/medline PY - 2020/7/4/entrez KW - Myf5 KW - Pax7 KW - WNT agonist KW - iPSC KW - muscular dystrophy KW - muslce stem cells KW - myogenic differentiation KW - pluripotent stem cells SP - 80 EP - 94 JF - Stem cell reports JO - Stem Cell Reports VL - 15 IS - 1 N2 - Duchenne muscular dystrophy (DMD) is a progressive and fatal muscle-wasting disease caused by DYSTROPHIN deficiency. Cell therapy using muscle stem cells (MuSCs) is a potential cure. Here, we report a differentiation method to generate fetal MuSCs from human induced pluripotent stem cells (iPSCs) by monitoring MYF5 expression. Gene expression profiling indicated that MYF5-positive cells in the late stage of differentiation have fetal MuSC characteristics, while MYF5-positive cells in the early stage of differentiation have early myogenic progenitor characteristics. Moreover, late-stage MYF5-positive cells demonstrated good muscle regeneration potential and produced DYSTROPHIN in vivo after transplantation into DMD model mice, resulting in muscle function recovery. The engrafted cells also generated PAX7-positive MuSC-like cells under the basal lamina of DYSTROPHIN-positive fibers. These findings suggest that MYF5-positive fetal MuSCs induced in the late stage of iPSC differentiation have cell therapy potential for DMD. SN - 2213-6711 UR - https://www.unboundmedicine.com/medline/citation/32619494/Induced_Fetal_Human_Muscle_Stem_Cells_with_High_Therapeutic_Potential_in_a_Mouse_Muscular_Dystrophy_Model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-6711(20)30225-3 DB - PRIME DP - Unbound Medicine ER -
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