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November 15, 2022

A novel method for generating naive human iPS cells with significantly higher differentiation potency

A joint research team led by Dr. Akira Kunitomi, a former postdoctoral fellow at CiRA (currently a researcher at the Gladstone Institute of Cardiovascular Disease), and ID Pharma Co., Ltd. has established a new method for naive iPS cell generation that uses a temperature-sensitive Sendai virus vector developed by the group to remove the vectors rapidly.

To date, only dermal fibroblasts have been successfully reprogrammed into naive iPS cells through generation methods using Sendai virus vectors and feeder cells. In a new study, the joint research group succeeded in generating naive iPS cells not only from human dermal fibroblasts but also from peripheral blood mononuclear cells by changing the combination of reprogramming genes.

The researchers subsequently created a temperature-sensitive Sendai virus vector that can be removed rapidly during the reprogramming process and established a feeder-free method to generate naive iPS cells from dermal fibroblasts using the modified Sendai virus vectors.

Furthermore, the group demonstrated that the naive iPS cells generated via the new method can better differentiate into trilineage and extra-embryonic trophectoderm than those derived by conventional methods because early removal of the Sendai virus vectors suppresses expression of exogenous genes.

Recently, naive human pluripotent stem cells have been widely used for studies on the early human embryos by taking advantage of their high pluripotency. The new protocol created in this study is expected to contribute to the development of such research and beyond.

Since the method can be applied to the establishment of primed human iPS cells, researchers will be able to obtain cell lines free of viral vector genomes without the time-consuming clone selection process. It is also expected that the new method will facilitate the generation of autologous iPS cells from donors and further advance studies on disease modeling, drug discovery, and cell therapy.

The results of this study were published online in Cell Reports Methods on October 17, 2022.

Paper Details
  • Journal: Cell Reports Methods
  • Title: Improved Sendai viral system for reprogramming to naive pluripotency
  • Authors: Akira Kunitomi1,2*, Ryoko Hirohata1,3, Vanessa Arreola2, Mitsujiro Osawa1,7, Tomoaki M. Kato1,3, Masaki Nomura1,3, Jitsutaro Kawaguchi4, Hiroto Hara4, Kohji Kusano4, Yasuhiro Takashima1, Kazutoshi Takahashi1, Keiichi Fukuda5, Naoko Takasu1,3 and Shinya Yamanaka1,2,3,6
    *: Corresponding author
  • Author Affiliations:
    1. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan
    2. Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA
    3. CiRA Foundation, Kyoto 606-8397, Japan
    4. ID Pharma Co., Ltd., Ibaraki 300-2611, Japan
    5. Department of Cardiology, Keio University School of Medicine, Tokyo 160-8582, Japan
    6. Department of Anatomy, University of California San Francisco, San Francisco, CA 94143, USA
    7. Present address: Thyas Co., Ltd., Kyoto 606-8501, Japan
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