It has been 15 years since Kyoto University Professor Shinya Yamanaka pioneered induced pluripotent stem cells (iPS cells). Much like fertilized eggs, iPS cells can transform into a variety of cells.
Remarkable developments continue, with research into applications for regenerative medicine and drug discovery, and the introduction of a “next generation type” with the potential to transform into a wider range of cells.
Recently, the possibility of applying iPS cell technology to improvements in the body's capabilities and prevention of aging has emerged.
Enabling Production of Placental Cells
First introduced in 2006, iPS cells are created by introducing a special gene into cells taken from the skin or blood of an organism, and “initializing” them into a fertilized egg-like state that can change and grow into a variety of cells.
When an egg and sperm meet to form a fertilized egg, the cells that will become the placenta are formed inside. Then, when the fertilized egg implants in the uterus, the placenta, which supplies oxygen and blood from the mother to the fetus, is formed. The state of the iPS cells is similar to that of a fertilized egg after implantation. Therefore, up to now they were unable to form a placenta, which requires the state of a fertilized egg before implantation.
Recently, however, an initialization process has been devised for production of a next-generation type iPS cell that is more similar to the fertilized egg before implantation. A Kyoto University research team announced in April that they have succeeded ー for the first time in the world ー in producing cells that form the basis of the placenta using this technology.
If conditions such as infertility, thought to be caused by abnormalities in the placenta, can be duplicated using these next-generation cells, they could help scientists understand the cause of such conditions.
In addition, because these cells are considered to be equally suitable to changing into any type of cell, they are one step closer to “totipotency,” which further expands their range of potential applications.
A number of studies on clinical application in regenerative medicine, in which cells and tissues made from iPS cells are transplanted for treatment, are also underway.
Developments related to eye diseases have been quick. Since 2014, RIKEN and the Kobe City Eye Hospital have been transplanting retinal cells to patients with three different diseases. Osaka University has also conducted transplants of corneal cells.
Other surgeries have been performed to transplant nerve cells into patients with Parkinson's disease (Kyoto University), platelets into patients with aplastic anemia (Kyoto University), heart muscle cell sheets into patients with severe heart failure (Osaka University), and immune cells into patients with head cancers (Chiba University).
They are also helping to combat COVID-19. Kyoto University announced in April that it had discovered candidate treatment drugs using iPS cells. They administered 500 existing drugs to human iPS cells to determine whether or not they could prevent the invasion of a virus, one with a similar mechanism of infection to COVID-19, but safer. They found that a drug for osteoporosis and a hypoglycemic agent had promising effects.
The issue is cost. According to the iPS Cell Research Foundation of Kyoto University, which stores and supplies cells, it costs about ￥40 million JPY (about $370,000 USD) to produce iPS cells from the blood of one healthy person.
It then costs between ￥60 million and ￥100 million JPY ($550,000 to about $1 million USD) to transform these into various types of cells for transplantation into one person.
This high cost arises because work is done completely by hand and requires an enormous amount of time. The foundation is hurrying to automate and streamline the production process and hopes to reduce the cost of the entire process from creation to transformation to about ￥3 million JPY ($28,000 USD) by 2025.
Direct Modification of Cells in the Body
The body’s immune system, which prevents the invasion of viruses and other pathogens, is different for each person. The iPS cells to be transplanted also have various immunotypes. If the body and cell types do not match, rejection reactions such as inflammation will occur.
The foundation prepares cells of several immunotypes, but, even so, only 40% of Japanese people have a matching type.
In 2020, the foundation began an initiative to use gene editing technology, which allows genes to be freely cut and pasted, to destroy the genes that determine the immunotype of iPS cells. When 12 genes are destroyed, rejection can allegedly be avoided in nearly every person in the world. The foundation aims to begin supplying these cells in 2022.
In recent years, “direct reprogramming” technology has also been gaining increasing attention. This technology aims to treat diseases and restore functions by introducing genes directly into cells in the body and transforming them into other cells.
Experiments conducted both in Japan and abroad have been successful in directly changing human skin cells into nerve cells, and blood vessel cells into intestinal cells. Since iPS cells are not involved, expectations are high for a simple and inexpensive way to treat diseases.
Kyoto University Professor Atsushi Takahashi points out, “After the invention of iPS cells, our understanding of the development of living organisms advanced dramatically, and the various cell initialization techniques developed have been very helpful.”
It sounds like science fiction, but it may be possible to strengthen the muscles of athletes to improve their athletic ability, or to increase nerve cells to improve memory for students sitting examinations. Likewise, we may be able to prevent aging by replacing deteriorating cells in the body with new, more vigorous cells.
(Find access to the special Sankei Shimbun report in Japanese at this link.)
Author: Juichiro Ito