December 22, 2017
Keio University School of Medicine
Japan Agency for Medical Research and Development
ID Pharma Co., Ltd.
A research group led by Senior Lecturer Masaki Ieda and Collaborative Researcher Kazutaka Miyamoto of the Department of Cardiology, Keio University School of Medicine, has succeeded in improving cardiac function by introducing three cardiogenic-inducing genes into the hearts of myocardial infarction model mice. This process efficiently, rapidly, and directly converts cardiac fibroblasts in the infarcted area into cardiomyocytes without damaging the cellular genome.
Dr. Ieda's group is conducting research on a new method of myocardial regeneration that does not require cell transplantation. This method involves introducing cardiogenic-inducing genes into non-myocardial cardiac fibroblasts present in the heart to directly generate myocardium. They have previously reported that by using a retroviral vector as a gene carrier, they could introduce three cardiogenic-inducing genes into cardiac fibroblasts in vivo in mice and directly generate cardiomyocytes. However, this previous method had challenges: 1) the potential for genomic damage due to the viral integration of the three genes during cardiac induction, and 2) low induction efficiency and the long time required for cardiomyocyte generation.
In this study, Dr. Ieda's group, in collaboration with ID Pharma Co., Ltd., developed a Sendai virus vector that simultaneously expresses the three cardiogenic-inducing genes (hereafter, cardiogenic Sendai virus vector). Using this cardiogenic Sendai virus vector, they succeeded in efficiently and rapidly generating cardiomyocytes directly from mouse and human fibroblasts in vitro (on culture dishes) without genomic damage. Furthermore, when the cardiogenic Sendai virus vector was introduced into the hearts of a mouse myocardial infarction model, they confirmed that myocardial regeneration began within one week, and cardiac function improved after one month.
The results of this study represent a new method of myocardial regeneration that does not require cell transplantation and is expected to be applied in the future to regenerative medicine for various heart diseases, including myocardial infarction and dilated cardiomyopathy. These research findings were published in the online early edition of the international scientific journal "Cell Stem Cell" on December 21, 2017 (U.S. Eastern Time).
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