A research team from the National Center for Child Health and Development (NCCHD) plans to apply to the government this fiscal year to conduct a clinical trial that would transplant liver cells generated from embryonic stem (ES) cells into infants with liver disease, The Yomiuri Shimbun has learned.
It would be the first clinical application performed in Japan using ES cells, which are a type of pluripotent cell.
The Tokyo-based NCCHD aims to develop liver cell products for use in regenerative medicine in about 2020.
ES cells are created by extracting cells from fertilized eggs that have not been used in fertility treatments, and culturing them. ES cells have the ability to proliferate without limit and can change into any type of cell desired. The cells can be used in regenerative medicine by transplanting them into an affected area to restore functions that have been lost.
The subjects of the clinical trial would be infants with severe hyperammonemia, a disease in which a particular enzyme does not function in the liver from birth. This causes ammonia to accumulate in the blood because it is not broken down properly. There are about 10 such patients nationwide every year. The disease can also interfere with consciousness and cause respiratory disorders.
From the age of 3 months, the disease can be treated through liver transplants, but some patients die before reaching that age.
In the study, Akihiro Umezawa, deputy director of the Research Institute, NCCHD; Mureo Kasahara, director of the Organ Transplantation Center, NCCHD; and other members of the team plan to transform pre-made ES cells into normal liver cells. Tens of millions of those cells would be sent to the liver via abdominal blood vessels within a few weeks after a baby’s birth.
The ES cell-derived liver cells would then break down ammonia and stabilize the patient’s condition so a liver transplant could be performed a few months later.
The clinical trial would involve five infants, with the team examining factors such as whether ammonia levels in the blood decreased adequately and whether liver cells were established in the liver.
The NCCHD is also considering partnering with corporations to develop products.
Induced pluripotent stem (iPS) cells, which like ES cells can be transformed into a variety of cells, can be manufactured by adding specific genes to certain cells, such as those in human skin or blood. They are not made from fertilized eggs but their quality can vary, so they need to be screened before they are used.
Many clinical trials on ES cells have been performed overseas, which is why the NCCHD decided ES cells were a safer choice. The NCCHD also designed its trial by taking into account their own prior research on the topic.
The trial has been approved by the NCCHD’s screening committee, which examines ethical aspects and other factors.