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May 02, 2022

Microwell bag culture for large-scale production of homogeneous islet-like cell clusters

The group led by Dr. Taro Toyoda has developed a novel bag culture method to produce homogeneous cell clusters on a large scale.

Islet transplantation is a promising therapeutic option for the treatment of Brittle type I diabetes. In general, 105-106 islets (clusters of endocrine cells) are required to treat one patient. However, size and quality heterogeneity of islets from donors, as well as a shortage of donors, has been one of the obstacles to the widespread use of this therapy. Although thousands of uniform-sized clusters can be produced using a conventional microwell plate, there are several unsuitable aspects for use in a cell manufacturing facility.

The Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA) group led by Dr. Taro Toyoda, CiRA Junior Associate Professor, and Toyo Seikan Group Holdings Ltd. teamed up to tackle the issue. Dr. Toyoda, Dr. Ryo Suenaga, a senior researcher at Toyo Seikan Group Holdings Ltd. and Dr. Shuhei Konagaya, a senior scientist at Orizuru Therapeutics, Inc., aimed to develop a novel bag culture method to produce homogeneous-sized cell clusters on a large scale (105-106 clusters). The group fabricated small-scale culture bags (<105 clusters) with microwells at the bottom and suitable holders for handling, and then investigated to decide critical culturing factors for homogeneity using undifferentiated iPS cells and iPS cell-derived pancreatic islet cells (iPIC). To obtain the number of cell clusters required for islet transplantation, the group designed a large-scale culture bag with microwells and succeeded in a production of 6.5×105 uniform iPIC clusters. This production method simplified the pre- and post-process of the culture--a degassing process before cell seeding and a cluster harvesting process.

The bag-based cluster production method developed in this study is expected to be advantageous for both clinical and research use in terms of scalability, sterility, and operability.

The results of this research were published online in the British scientific journal Scientific Reports on March 25, 2022 (GMT).

Paper Details
  • Journal: Scientific Reports
  • Title: Microwell bag culture for large-scale production of homogeneous islet-like clusters
  • Authors: Ryo Suenaga1*, Shuhei Konagaya2, Junji Yamaura3,5, Ryo Ito2, Satoshi Tanaka1, Yoichi Ishizaki1, and Taro Toyoda4,5*
  • Author Affiliations:
    1. Corporate Research & Development, Toyo Seikan Group Holdings, Ltd., Yokohama, Japan
    2. Orizuru Therapeutics, Inc., Kanagawa, Japan
    3. Cell Therapies, Pharmaceutical Science, Takeda Pharmaceutical Company Limited, Kanagawa, Japan
    4. Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
    5. Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA), Kanagawa, Japan
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