Japan is advancing research to apply induced pluripotent stem cell (iPSC) to treat heart diseases. After the world’s first-of-its-kind iPSC-based heart cell transplant in January, a second clinical trial has been approved this summer and the third is in the pipeline. Currently, cardiac insufficiency can only be cured by transplants but the waiting list for a donor is long. There are hopes that the new treatment will provide new alternatives in the future.
It was Osaka University that in January 2020 announced a first-of-its-kind successful transplantation of heart muscle cells grown from iPSCs. The surgery was conducted by the research team of Prof. Yoshiki Sawa targeting patients with ischemic heart diseases, a disease where local areas of the heart get damaged due to inadequate blood and oxygen supply caused by a blockage in blood vessels.
Their approach is to reprogram and grow hundreds of million heart muscle cells into a thin sheet using iPSCs and transplant them onto the surface of the human heart. This method enables the preparation of cardiomyocytes that can be stored in volumes. The shorter time required for cultivation allows the medical team to respond also to emergencies.
The research team at Keio University led by Prof. Keiichi Fukuda, which received the second approval from the Ministry of Health, Labor and Welfare in August, aims to treat patients suffering from dilated cardiomyopathy, a diseased condition where the heart swells up and fails to contract and pump efficiently. The team was granted approval for the treatment of 3 patients to conduct a transplantation of heart muscle cells derived from iPSCs. Specifically, they transform iPSCs into 3 dimensional (3D) cardiomyocyte spheroid, which is a tiny ball of heart muscle cells clustered together. These spheroids are injected into the heart using a new injection device, which showed optimal distribution and favorable retention of functional cells in an animal study.
Meanwhile, iHeart Japan Corp., a Kyoto University spin-off, announced in May that a university hospital team is planning a similar clinical trial and is scheduled to submit the plans to the Minister of Health. Here, the team of Prof. Kenji Minatoya uses multi-layered sheet-shaped heart muscle cells to target both, ischemic heart disease and dilated cardiomyopathy.
IPSCs are cells reprogrammed to an embryonic-like state that can then be directed to grow into almost any other cell type. Therefore, they have become a promising cell source for regenerative medicine, such as for cardiovascular therapies.
According to a study by the World Health Organization, ischemic heart disease was the top cause of death in the world. In Japan, heart failure is the No.2 cause of death, only after cancer.