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May 30, 2022

Invention of technology to create mature skeletal muscle cells from iPS cells without genetic manipulation

The group led by Dr. Hidetoshi Sakurai has established a technique to generate mature muscle cells from human iPS cells without genetic transfer. These muscle cells could contribute to the elucidation of pathological conditions and drug screening.

Muscle diseases often have abnormal internal cellular structures such as triads and sarcomeres, and it is considered important to create mature skeletal muscle cells with these structures in order to accurately reproduce the pathological conditions. Furthermore, it is desirable for the skeletal muscle cells to be physiological cells that closely resemble human muscle fibers. Several groups, including this research group, have succeeded in maturing skeletal muscle cells, but the methods require special equipment and devices, and further technological innovation is needed to apply them to drug screening.

In the past, skeletal muscle cells have been generated efficiently from human iPS cells by introducing specific genes and inducing differentiation. However, this method may result in the formation of unnatural gene networks due to the amplification of specific gene expression, which may adversely affect the pathological analysis of skeletal muscle diseases.

An academic-industry collaboration led by Associate Professor Hidetoshi Sakurai (CiRA, Kyoto University) has developed a technology to induce skeletal muscle stem cells from human iPS cells without using gene transfer and create skeletal muscle cells from the iPS cell-derived stem cells. Compared to the skeletal muscle cells made by previously reported methods, the cells generated in this study are very mature with intracellular structures characteristic of skeletal muscle, which may lead to the patient iPS cell-based analysis of pathophysiological mechanisms of muscle diseases. Furthermore, the skeletal muscle cells generated by this induction system have a high differentiation rate and uniformity, and are expected to used for drug screening and contribute to drug development.

The results of this research were published online in the Swiss scientific journal "Frontiers in Cell and Developmental Biology" on May 30, 2022.

Paper Details
  • Journal: Frontiers in Cell and Developmental Biology
  • Title: Mature myotubes generated from human induced pluripotent stem cells without forced gene expression
  • Authors: Kei Fujiwara1, Risa Yamamoto2, Tomoya Kubota2, Atsutoshi Tazumi3, Tomoka Sabuta1, Masanori P. Takahashi2 and Hidetoshi Sakurai1*
  • Author Affiliations:
    1. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto
    2. Clinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Division of Health Sciences, Osaka University Graduate School of Medicine
    3. Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation
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