A research group at Keio University School of Medicine has developed a method for producing high-purity cardiomyocytes, which are the muscles of the heart, from human iPS cells.As a technology that can produce safer cardiomyocytes easily and relatively inexpensively, we plan to apply for clinical research to the on-campus committee in the future.

 Cardiomyocytes make the myocardium, which is indispensable for the heart to send blood to the whole body, but if it is lost due to illness, it cannot be regenerated in mammals and the contractile force of the myocardium is reduced.

 In regenerative medicine, pluripotent stem cells such as ES cells and iPS cells, which are said to have the ability to differentiate into all somatic cells, are attracting attention.However, it was difficult to induce the differentiation of all undifferentiated stem cells into the target cells, and the problem was that the cells that could cause tumors were mixed in the cells that could not be differentiated.

 Research groups such as Assistant Professor Shugo Toyama, Specially Appointed Lecturer Atsushi Fujita, Professor Keiichi Fukuda, and Professor Makoto Suematsu (currently Chairman of the Japan Agency for Medical Research and Development) of the same university have active glucose consumption in undifferentiated stem cells. , It has been clarified that myocardial cells use lactic acid as an energy source, and we have reported a method of removing glucose from the culture solution and adding lactic acid to remove undifferentiated stem cells.However, this alone took time for the undifferentiated stem cells to completely die.

 Therefore, this time, we focused on four amino acids, glutamine, arginine, serine, and glycine, which are actively consumed by undifferentiated cells together with glucose.When human ES / iPS cells were cultured in a culture medium from which these four and glucose had been removed, it was found that they died dramatically compared to when they were not removed.
Next, glucose and glutamine, which are essential for cell survival, are removed from the culture medium, and instead, lactic acid, which is an energy source for cardiomyocytes, is added to theoretically "undifferentiated stem cells cannot survive, only cardiomyocytes can survive" environment. It was confirmed that undifferentiated stem cells were completely killed and only cardiomyocytes could be selected alive.

 In this research, it became possible to produce high-purity cardiomyocytes by a simple and relatively low-cost process of "changing to a special culture solution".When performing cardiac regenerative medicine using cardiomyocytes differentiated from human iPS cells, it is expected to be an important technology for obtaining a large amount of highly safe cardiomyocytes.

Keio University

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