2020/09/08
Keio University School of Medicine
Japan Agency for Medical Research and Development (AMED)
A research group led by Project Lecturer Shugo Tohyama of the Department of Cardiology, Keio University School of Medicine, and Assistant Professor Sho Tanosaki of the Department of Emergency and Critical Care Medicine, in collaboration with research groups led by Professor Makoto Suematsu of the Department of Biochemistry, Professor Minoru Ko of the Department of Systems Medicine, and Lipidome Lab Co., Ltd., has succeeded in creating safer cells for transplantation by efficiently removing undifferentiated iPS cells, which are a cause of tumorigenesis and a challenge for clinical application, from a population of differentiated cells derived from human iPS cells.
Human induced pluripotent stem cells (human iPS cells) hold promise for the realization of "regenerative medicine," which involves transplanting therapeutic cells created outside the body, due to their pluripotency, meaning they can theoretically differentiate into all cell types that make up the body. However, inducing all human iPS cells to differentiate into the desired cell type is difficult, and the persistence of cells that fail to differentiate and can cause tumor formation has been a major challenge for the realization of regenerative medicine in various fields.
The joint research group has now discovered that fatty acid synthesis is actively occurring in human iPS cells and has clarified that it plays a crucial role in their proliferation and survival. By leveraging this characteristic, they have successfully established a method to selectively kill only the undifferentiated iPS cells that cause tumor formation and to sort out living differentiated cells, such as cardiomyocytes and nerve cells differentiated from human iPS cells, by inhibiting fatty acid synthesis using orlistat, a drug approved by the FDA (U.S. Food and Drug Administration) as an anti-obesity treatment. This makes it possible to produce high-purity cardiomyocytes for clinical application through an extremely simple process. This research is expected to solve the major challenge of producing highly safe cells for transplantation and to significantly accelerate the realization of regenerative medicine in various fields.
This research was published in the American scientific journal "iScience," issued by Cell Press, on September 5, 2020 (U.S. Eastern Time).
Please see below for the full press release.