April 15, 2022
Elimination of non-target cells mixed into islet-like cells generated from human iPS cells based on characterization
The transplantation of islet-like endocrine cells derived from human pluripotent stem cells, such as ES cells and iPS cells, is expected to be a curative treatment for diabetes. Producing the islet-like endocrine cells artificially causes contamination of non-endocrine cells, and keeping the contamination minimal is inevitable when a large amount of cells are produced for cell transplantation. However, because the non-endocrine cells are very rare and form small populations, it has been difficult to characterize them.
An academic-industry collaboration led by CiRA Junior Associate Professor Taro Toyoda has identified the non-endocrine cells that may be contaminated in the manufacturing process and detect them with high sensitivity, by analyzing gene expression of human iPS cell-derived pancreatic islet-like cells at the single-cell level.
In addition, as novel methods for removing non-target cells, the researchers showed that inhibition of PLK molecules, which are involved in cell proliferation, and inhibition of the glycolytic system are effective. These findings are expected to be useful in the safer mass production of human iPS cell-derived islet-like cells for cell therapy in combination with existing methods to remove non-target cells.
The findings were published online in the British scientific journal Scientific Reports on 18 March 2022 (GMT).
- Journal: Scientific Reports
- Title: Characterization and reduction of non-endocrine cells accompanying islet-like endocrine cells differentiated from human iPSC
- Authors: Hideyuki Hiyoshi1,3,#, Kensuke Sakuma1,3,4,#, Noriko Tsubooka-Yamazoe1,3,4,#, Shinya Asano5, Taisuke Mochida1,3, Junji Yamaura3,6, Shuhei Konagaya2,3,4, Ryo Fujii5, Hirokazu Matsumoto1,3,
Ryo Ito1,3,4 and Taro Toyoda2,3
- Author Affiliations:
- T-CiRA Discovery, Research, Takeda Pharmaceutical Company Limited, Kanagawa, Japan
- Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
- Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA), Kanagawa, Japan
- Orizuru Therapeutics, Inc, Kanagawa, Japan
- Axcelead Drug Discovery Partners, Inc, Kanagawa, Japan
- Pharmaceutical Science, Takeda Pharmaceutical Company Limited, Kanagawa, Japan