A muscle fatigue-like contractile decline was recapitulated using skeletal myotubes from Duchenne muscular dystrophy patient-derived iPSCs
Summary: Duchenne muscular dystrophy (DMD) is a muscle degenerating disease caused by dystrophin deficiency, for which therapeutic options are limited. To facilitate drug development, it is desirable to develop in vitro disease models that enable the evaluation of DMD declines in contractile perform...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | Cell Reports Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379121001312 |
| _version_ | 1818457546565877760 |
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| author | Tomoya Uchimura Toshifumi Asano Takao Nakata Akitsu Hotta Hidetoshi Sakurai |
| author_facet | Tomoya Uchimura Toshifumi Asano Takao Nakata Akitsu Hotta Hidetoshi Sakurai |
| author_sort | Tomoya Uchimura |
| collection | DOAJ |
| description | Summary: Duchenne muscular dystrophy (DMD) is a muscle degenerating disease caused by dystrophin deficiency, for which therapeutic options are limited. To facilitate drug development, it is desirable to develop in vitro disease models that enable the evaluation of DMD declines in contractile performance. Here, we show MYOD1-induced differentiation of hiPSCs into functional skeletal myotubes in vitro with collagen gel and electrical field stimulation (EFS). Long-term EFS training (0.5 Hz, 20 V, 2 ms, continuous for 2 weeks) mimicking muscle overuse recapitulates declines in contractile performance in dystrophic myotubes. A screening of clinically relevant drugs using this model detects three compounds that ameliorate this decline. Furthermore, we validate the feasibility of adapting the model to a 96-well culture system using optogenetic technology for large-scale screening. Our results support a disease model using patient-derived iPSCs that allows for the recapitulation of the contractile pathogenesis of DMD and a screening strategy for drug development. |
| first_indexed | 2024-12-14T22:44:17Z |
| format | Article |
| id | doaj.art-a98b172c9ae7485fa19e9f5ec8956971 |
| institution | Directory Open Access Journal |
| issn | 2666-3791 |
| language | English |
| last_indexed | 2024-12-14T22:44:17Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports Medicine |
| spelling | doaj.art-a98b172c9ae7485fa19e9f5ec89569712022-12-21T22:44:53ZengElsevierCell Reports Medicine2666-37912021-06-0126100298A muscle fatigue-like contractile decline was recapitulated using skeletal myotubes from Duchenne muscular dystrophy patient-derived iPSCsTomoya Uchimura0Toshifumi Asano1Takao Nakata2Akitsu Hotta3Hidetoshi Sakurai4Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Takeda-CiRA Joint Program, Fujisawa, Kanagawa 251-8555, Japan; Corresponding authorDepartment of Cell Biology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; The Center for Brain Integration Research, Tokyo Medical and Dental University, Tokyo 113-8510, JapanDepartment of Cell Biology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; The Center for Brain Integration Research, Tokyo Medical and Dental University, Tokyo 113-8510, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Takeda-CiRA Joint Program, Fujisawa, Kanagawa 251-8555, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Takeda-CiRA Joint Program, Fujisawa, Kanagawa 251-8555, Japan; Corresponding authorSummary: Duchenne muscular dystrophy (DMD) is a muscle degenerating disease caused by dystrophin deficiency, for which therapeutic options are limited. To facilitate drug development, it is desirable to develop in vitro disease models that enable the evaluation of DMD declines in contractile performance. Here, we show MYOD1-induced differentiation of hiPSCs into functional skeletal myotubes in vitro with collagen gel and electrical field stimulation (EFS). Long-term EFS training (0.5 Hz, 20 V, 2 ms, continuous for 2 weeks) mimicking muscle overuse recapitulates declines in contractile performance in dystrophic myotubes. A screening of clinically relevant drugs using this model detects three compounds that ameliorate this decline. Furthermore, we validate the feasibility of adapting the model to a 96-well culture system using optogenetic technology for large-scale screening. Our results support a disease model using patient-derived iPSCs that allows for the recapitulation of the contractile pathogenesis of DMD and a screening strategy for drug development.http://www.sciencedirect.com/science/article/pii/S2666379121001312EFS trainingmuscle overuseoptogeneticshigh-throughputinduced pluripotent stem cellsskeletal muscle cells |
| spellingShingle | Tomoya Uchimura Toshifumi Asano Takao Nakata Akitsu Hotta Hidetoshi Sakurai A muscle fatigue-like contractile decline was recapitulated using skeletal myotubes from Duchenne muscular dystrophy patient-derived iPSCs Cell Reports Medicine EFS training muscle overuse optogenetics high-throughput induced pluripotent stem cells skeletal muscle cells |
| title | A muscle fatigue-like contractile decline was recapitulated using skeletal myotubes from Duchenne muscular dystrophy patient-derived iPSCs |
| title_full | A muscle fatigue-like contractile decline was recapitulated using skeletal myotubes from Duchenne muscular dystrophy patient-derived iPSCs |
| title_fullStr | A muscle fatigue-like contractile decline was recapitulated using skeletal myotubes from Duchenne muscular dystrophy patient-derived iPSCs |
| title_full_unstemmed | A muscle fatigue-like contractile decline was recapitulated using skeletal myotubes from Duchenne muscular dystrophy patient-derived iPSCs |
| title_short | A muscle fatigue-like contractile decline was recapitulated using skeletal myotubes from Duchenne muscular dystrophy patient-derived iPSCs |
| title_sort | muscle fatigue like contractile decline was recapitulated using skeletal myotubes from duchenne muscular dystrophy patient derived ipscs |
| topic | EFS training muscle overuse optogenetics high-throughput induced pluripotent stem cells skeletal muscle cells |
| url | http://www.sciencedirect.com/science/article/pii/S2666379121001312 |
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