From Bio Journal - May 2019

iPS cells and genome editing accelerate organ transplants

Since MEXT has taken the stance of permitting the production of human organs for transplantation using animal-human chimeric embryos (see BJ April 2019), the organ transplant world has begun to move into areas that were once considered taboo.

On April 5, the Jikei University Hospital in Tokyo and Sumitomo Dainippon Pharma Co., Ltd announced that they had produced tissues that could be transformed into kidneys through the use of induced pluripotent stem (iPS) cells and pig embryo tissues and were making efforts toward kidney regeneration treatments that would grow into kidneys after transplanting into patients. The procedure is as follows. Firstly, iPS cells are produced from the patient's own cells, etc. Tissues that will grow into a kidney are then removed from the pig embryo and iPS cells injected into the tissues to produce a kidney seed. The seed is then transplanted into the patient. When the seed has grown into a kidney, it is connected to the urinary duct and made to function. In this case, there is a strong possibility that genome editing technology will be used to remove pig-originating viruses. (Chunichi Shimbun 6 April 2019)

In a separate development, the Japan Association of Medical Sciences (JAMS) has initiated moves toward uterus transplants, also previously considered taboo. On April 3, JAMS established a committee to investigate reproductive and transplant medicine in a move toward lifting the ban on uterus transplants. The committee will also look into whether or not to recognize surrogate birth. The committee is expected to reach a conclusion on these issues within two years. In November 2018, Keio University submitted a clinical research plan aimed at uterus transplants between close relatives to the Japan Society of Obstetrics and Gynecology (JSOG). Tokyo Women's Medical University has also begun experiments on uterus transplants using monkeys. The aim is to implant a fertilized ovum produced by in vitro fertilization into a uterus transplanted into another monkey inducing pregnancy and birth of a baby monkey. It is thought that the appearance of these moves is what caused JAMS to initiate investigations. (Mainichi Shimbun 4 April 2019)

The applications of iPS cells are also spreading. On March 5, MHLW approved a plan for the transplantation of corneal cells produced from iPS cells submitted by Osaka University. The subjects of the transplantations are four patients suffering from corneal skin stem cell fatigue syndrome. (Asahi Shimbun 6 March 2019)

Problems have previously occurred with transplant operations involving the eye and using iPS stem cells. In January 2018, when the Kobe City Medical Center General Hospital transplanted a retina produced using iPS cells into a patient suffering from wet age-related macular degeneration, retinal edema occurred. iPS cell transplants are still at the stage of experiments on human guinea pigs.

On 23 February, it was reported in the media that Yokohama City University planned to apply as early as the summer of this year to produce a mini-liver from iPS cells for transplantation into human babies. The idea is to produce three types of cells, liver progenitor cells, vascular endothelial cells (cells that form the inner lining of blood vessels), and mesenchymal cells (found in bone marrow) from iPS cells, combine these to produce a mini-liver to be mass transplanted into babies suffering from ornithine transcarbamylase (OTC) deficiency (an inherited disorder which causes toxic levels of ammonia to build up in the blood due to inability to decompose that substance) in order to supplement the function of the liver. (Asahi Shimbun 2 February 2019) To suppress rejection, the greatest barrier to organ transplantations, the marker gene on the surface of the donated organ cell, which immune cells detect as foreign material, will be destroyed by genome editing technology, thus not allowing the donated organ to be recognized as foreign material. In this and other ways, the appearance of genome editing technology is likely to cause transplant medicine to move forward at a rapid pace.

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