2024/04/26
Shinshu University
Keio University
Heartseed Inc.
A research group including Professor Yuji Shiba from the Department of Regenerative Medical Science and Professor Koichiro Kuwahara from the Department of Cardiovascular Medicine at the Shinshu University School of Medicine (hereinafter, Shinshu University), and Lecturer Shugo Tohyama and Professor Emeritus Keiichi Fukuda from the Division of Cardiology at the Keio University School of Medicine (hereinafter, Keio University), has succeeded in a joint research project with Heartseed Inc. The team generated cardiomyocyte spheroids from clinical-grade human induced pluripotent stem cells (iPS cells) and transplanted them into the hearts of cynomolgus monkeys with myocardial infarction. The results showed that the transplanted cardiomyocytes engrafted long-term and restored the monkeys' cardiac function. They also demonstrated that the incidence of post-transplantation ventricular arrhythmia, a common side effect, was significantly lower compared to previous reports.
In severe conditions such as myocardial infarction, hundreds of millions of cardiomyocytes are lost. However, mammals, including humans, do not have the innate ability to regenerate these lost heart muscle cells. Because human iPS cells are pluripotent and can theoretically differentiate into all cell types in the body, they hold great promise for realizing "regenerative medicine" for such diseases, which involves transplanting therapeutic cells created *in vitro*. However, the occurrence of ventricular arrhythmias after the transplantation of cardiomyocytes differentiated from human iPS cells has been a major hurdle to its practical application.
In this study, the joint research group first produced highly purified cardiomyocytes (mainly ventricular muscle) from clinical-grade human iPS cells using a clinical-grade culture medium, and then created microscopic myocardial tissue clusters (cardiomyocyte spheroids). Upon transplanting these cardiomyocyte spheroids into cynomolgus monkeys with myocardial infarction, the transplanted cardiomyocytes successfully engrafted long-term and restored the monkeys' cardiac function. They also revealed that the incidence of post-transplantation ventricular arrhythmias, a side effect, was significantly lower compared to previous reports.
These research findings are expected to solve the major challenge of post-transplantation ventricular arrhythmias and greatly accelerate the realization of cardiac regenerative medicine. Furthermore, based on these findings, a clinical trial in humans (the LAPiS trial) has already been initiated. The results of this study were published in the online edition of "Circulation," a scientific journal of the American Heart Association, on April 26, 2024, at 5:00 PM (U.S. Eastern Time).
Shinshu University Press Release
For the full press release, please see below.