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Upload organization:Japanest NIPPON   Upload date:2013/04/23

Shinya Yamanaka, M.D.,Ph.D., Kyoto University | New Frontiers in Regenerative Medicine – iPS Cell Research

Induced pluripotent stem (iPS) cells are revolutionizing regenerative medicine and the treatment of catastrophic illnesses. The medical world is keeping a close eye on advances in iPS cell research, and there is great anticipation of the potential practical use of these cells.
Currently, in 2013, a clinical research project is about to start on iPS cell–derived retina cell transplantation in patients with age-related macular degeneration. This will be the very first attempted clinical application of iPS cells. The 2012 Nobel Prize in Physiology and Medicine was awarded for work conducted in iPS cell research, prompting increased public interest in the field. There have also been reports that, in Japan, the field is to receive more research funding. Researchers must capitalize on this trend and continue to make steady progress in advancing iPS cell research.

Continued public interest in iPS cells and regenerative medicine will ensure that talented young scientists will enter the field to maintain the impetus of the research, and it is expected to bring more support to this field that is changing the future of medicine.

iPS cells are somatic cells that have pluripotency, in other words the ability to differentiate into a wide variety of cells through the transfection of several types of gene, and also the ability to self-replicate and maintain their properties after cell division. iPS cell–related research is considered to be of utmost importance in regenerative medicine, and researchers around the world are competing fiercely for breakthrough results. 

When iPS cells were first generated, from mouse fibroblasts, in 2006, a type of virus was used to deliver the genes for transfection. This was a cause of great concern, however, because of the risk that the virus could harm the genes and trigger cancer formation as it delivers them into the cell chromosomes. In addition, the success rate was extremely low; out of about 100,000 somatic cells, only 0 to 2 iPS cells were generated.

More recently, however, researchers have succeeded in developing a method to generate iPS cells by having a plasmid, which is a ring-shaped DNA molecule that breaks down inside cells after a short period of time, carry the four genes for transfection, thereby reducing the chances of cancer formation. Moreover, the success rate of this method is about 30 times that of previous methods. This method was first published in the online edition of Nature Methods on April 4, 2011.

How are iPS cells expected to benefit our lives? Of primary interest is their potential application in regenerative medicine.

Multicellular organisms are typically made up of many building blocks, which are in turn made up of smaller building blocks; an individual is made up of organs, which are made up of tissue, which are made up of cells. For example, an adult human being is composed of 60 trillion cells. These cells can be classified into 200 different types, such as neurons, T helper cells, and osteoblasts. Different types of human cells have different functions, and one type of cell cannot take the place of another. Furthermore, one type of cell cannot transform into another.

Consequently, if an internal organ were partially damaged or stopped functioning, the standard medical treatment would be to perform an organ transplant or to implant an artificial organ. 
However, there are many unresolved issues regarding these treatments. To give a few examples, the number of organ donors is extremely limited, transplant rejection may occur, and artificial organs do not quite match the intricacy of actual organs.

For this reason, regenerative medicine is garnering attention as a potential game-changer for the field of medicine. Regenerative medicine aims to repair and revive organs and tissues damaged by illness or injury through the use of artificially grown cells and tissue.

The Past and the Future of iPS Cells
Regenerative medicine offers many merits compared to conventional medicine. Among all the topics in regenerative medicine, why is iPS regarded as the most important?

Before the discovery of iPS cells, research was being conducted on embryonic stem (ES) cells as cells with pluripotency and self-replicating abilities.
Although the strict ethical requirements put in place by the Japanese government presented challenges to research, nevertheless, in 2003, Professor Norio Nakatsuji of Kyoto University became the first person to establish a method to generate human ES cell lines from fertilized embryos, and established a system to distribute human ES cell lines to other researchers.
ES cells are stem cells derived from the inner cell mass of an early-stage embryo in the blastocyst stage. It was hoped that these cells could have medical applications, but the risk of transplant rejection remained, and the destruction of human embryos raised ethical issues; the practical application of ES cells, therefore, was thought to be extremely difficult.

Then came iPS cells. iPS cells can be generated from fibroblasts in adult human skin cells. These cells eliminate the ethical issue of destroying embryos, the seeds of life, and greatly reduce the risk of transplant rejection. For this reason, they are expected to be used in cell transplantation therapies. Additionally, the scope of their applications is widening; for example, they can be used to evaluate the safety of medications.

Towards the Advancement of iPS Cell Research
The Center for iPS Cell Research and Application at Kyoto University strives to generate disease-specific iPS cells derived from patients with genetic diseases or intractable diseases of unknown causes, and to have these cells differentiate into tissue that is difficult to obtain otherwise to better understand the patients’ conditions in vitro. In addition, the Center has initiated research on drug discovery using disease-specific iPS cells, which will lead to the development of new therapies and drugs.

Worldwide competition is fierce in the field of iPS cell research, not only in terms of breakthrough results, but also with regard to securing intellectual property rights.
The patent for the world’s first iPS cell, generated in 2006, was transferred to Kyoto University from an American company in January 2011, and was registered with the European Patent Office in August 2011. Kyoto University also plans to register the patent with 17 European countries, including the United Kingdom, Germany, and France. These patents will also cover iPS cells yet to be discovered, provided they are structurally similar, and therefore can be considered as being of the same family. Such action is in anticipation of the fact that, as academic knowledge deepens and technology advances, the competition for patents will only intensify.

For Japan to become the world leader in iPS cell research in name and substance alike, ample funding and a top-quality research environment are a must. These are absolute requirements for iPS research to be able to make a contribution to improving the lives of people at large.