Although there are key players in markets like the U.S., Australia, and the EU, Japan continues to accelerates its position as a hub for induced pluripotent stem cell (iPS cell) therapy with generous funding, acquisitions, and strategic partnerships.
Induced Pluripotent Stem Cells (iPS Cells)
Pluripotent stem cells are cells that are capable of developing into any type of cell or tissue in the human body. These cells have the capability to replicate and help in repairing damaged tissues within the body. In 2006, the Japanese scientist Shinya Yamanaka demonstrated that an ordinary cell can be turned into a pluripotent cell by genetic modification. These genetically reprogrammed cells are known as induced pluripotent cells, also called iPS cells or iPSCs.
In this article:
- iPS Cells Definition
- iPS Cell Applications
- iPS Cells Japan
- iPS Cell Therapy
- iPS Cells Discovery
- iPS Cells Advantages and Disadvantages
- iPS Cell Trial – Cynata Therapeutics and Fujifilm
- iPS Cells Technology
iPS Cells Definition
An induced pluripotent stem cell (iPS cell) is a type of pluripotent stem cell that has the capacity to divide indefinitely and create any cell found within the three germ layers of an organism. These layers include the ectoderm (cells giving rise to the skin and nervous system), endoderm (cells forming gastrointestinal and respiratory tracts, endocrine gland, liver, and pancreas), and mesoderm (cells forming bones, cartilage, most of the circulatory system, muscles, connective tissues, and other related tissues.).
iPS cells have significant potential for therapeutic applications. For autologous applications, the cells are extracted from the patient’s own body, making them genetically identical to the patient and eliminating the issues associated with tissue matching and tissue rejection.
iPS Cell Applications
iPS cells have the potential to be used to treat a wide range of diseases, including diabetes, heart diseases, autoimmune diseases, and neural complications, such as Parkinson’s disease, Alzheimer’s disease.
Importantly, iPS cells are being explored for their use in:
- Cell therapy applications
- Drug development and discovery
- Toxicology testing
- Disease modelling
- Personalized medicine
iPS Cells Japan
Over the past few years, Japan has accelerated its position as a hub for regenerative medicine research, largely driven by support from Prime Minister Shinzo Abe who has identified regenerative medicine and cellular therapy as key to the Japan’s strategy to drive economic growth.
The Prime Minister has encouraged a growing range of collaborations between private industry and academic partners through an innovative legal framework approved last fall.
He has also initiated campaigns to drive technological advances in drugs and devices by connecting private companies with public funding sources. The result has been to drive progress in both basic and applied research involving induced pluripotent stem cells (iPS cells) and related stem cell technologies.
2013 was a landmark year in Japan, because it saw the first cellular therapy involving transplant of iPS cells into humans initiated at the RIKEN Center in Kobe, Japan. Led by Masayo Takahashi of the RIKEN Center for Developmental Biology (CDB). Dr. Takahashi and her team were investigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration.
To speed things along, RIKEN did not seek permission for a clinical trial involving iPS cells, but instead applied for a type of pretrial clinical research allowed under Japanese regulations. The RIKEN Center is Japan’s largest, most comprehensive research institution, backed by both Japan’s Health Ministry and government.
iPS Cell Therapy
This “pretrial clinical research” allowed the RIKEN research team to test the use of iPS cells for the treatment of wet-type age-related macular degeneration (AMD) on a very small scale, in only a handful of patients. Unfortunately, the study was suspended in 2015 due to safety concerns. As the lab prepared to treat the second trial participant, Yamanaka’s team identified two small genetic changes in the patient’s iPSCs and the retinal pigment epithelium (RPE) cells derived from them.
However, in June 2016 RIKEN Institute announced that it would be resuming the clinical study involving the use of iPSC-derived cells in humans. According to the Japan Times, this second attempt at the clinical study is using allogeneic rather than autologous iPSC-derived cells, because of the greater cost and time efficiencies.
Specifically, the researchers will be developing “retinal tissues from iPS cells supplied by Kyoto University’s Center for iPS Cell Research and Application,” an institution headed by Nobel prize winner Shinya Yamanaka.
iPS Cells Discovery
Japan has a unique affection for iPS cells, as the cells were originally discovered by the Japanese scientist, Shinya Yamanaka of Kyoto University. Mr. Yamanaka was awarded the Nobel Prize in Physiology or Medicine for 2012, an honor shared jointly with John Gurdon, for the discovery that mature cells can be reprogrammed to become pluripotent.
In addition, Japan’s Education Ministry said it’s planning to spend 110 billion yen ($1.13 billion) on induced pluripotent stem cell research during the next 10 years, and the Japanese parliament has been discussing bills that would “speed the approval process and ensure the safety of such treatments.”
In April, Japanese parliament even passed a law calling for Japan to make regenerative medical treatments like iPSC technology available for its citizens “ahead of the rest of the world.” If those forces were not enough, Masayo Takahashi of the RIKEN Center for Developmental Biology in Kobe, Japan, who is heading the world’s first clinical research using iPSCs in humans, was also chosen by the journal Nature as one of five scientists to watch in 2014.
iPS Cell Advantages and Disadvantages
Clearly, Japan is the global leader in iPS cell technologies and therapies. However, progress with stem cells has not been without setbacks within Japan, including a recent scandal at the RIKEN Institute that involved falsely manipulated research findings and a hold on the first clinical trial involving transplant of an iPS cell product into humans.
Nonetheless, Japan has emerged from these troubles to become the most liberalized nation pursuing the development of iPS cell products and services.
iPS cells represent one of the most promising advances within the field of stem cell research, because of their diverse ability to differentiate into any of the approximately 200 cell types that compose the human body.
Even though there is growing evidence to support the safety of iPS cells within cell therapy applications, some people remain concerned that patients who receive implants of iPS derived cells might be at risk of cancer, as genetic manipulation is required to create the cell type.
iPSC Trial – Cynata Therapeutics and Fujifilm
In a world-first, Cynata Therapeutics (ASX:CYP) received approval in September 2016 to launch a clinical trial in the UK with the world’s first first formal clinical trial of an allogeneic iPSC-derived cell product, which it calls “CYP-001.” The study involves centers in both the UK and Australia.
In this landmark trial, the Australian regenerative medicine company is testing an iPS cell-derived mesenchymal stem cell (MSC) product for the treatment of Graft-vs-Host-Disease (GvHD). Not surprisingly, the Japanese conglomerate Fujifilm is also involved with this historic trial.
Headquartered in Tokyo, Fujifilm is one of the largest players in regenerative medicine field and has invested significantly into stem cells through their acquisition of Cellular Dynamics International (CDI). Additionally, Fujifilm has invested in Japan Tissue Engineering Co. Ltd. (J-Tec), giving it a broad base in regenerative medicine across multiple therapeutic areas.
iPS Cell Technology
For a young company like Cynata, having validation from an industry giant like Fujifilm is a huge boost. As stated by Cynata CEO, Dr. Ross Macdonald, “The decision by Fujifilm confirms that our technology is very exciting in their eyes. It is a useful yardstick for other investors as well. Of course, the effect of the relationship with Fujifilm on our balance sheet is also important.”
If Fujifilm exercises their option to license Cynata’s GvHD product, then the costs of the product and commercialization will become the responsibility of Fujifilm. Cynata would also receive milestone payments from Fujifilm of approximately $60M AUS and a double-digit royalty payment.
Cynata was also the first to scale-up manufacture of an allogeneic cGMP iPS celll line. It sourced the cell line from Cellular Dynamics International (CDI) when CDI was still an independent company listed on NASDAQ. In April 2015, CDI was subsequently acquired by Fujifilm, who as mentioned, is a major shareholder in Cynata and its strategic partner for GvHD.
Although Cynata is showing promising early-stage data from its GvHD trial, methods for commercializing iPS cells are still being explored and clinical studies investigating iPS cells remain extremely low in number.
To learn more, view the “Global Induced Pluripotent Stem Cell (iPSC) Industry Report.”
 Dvorak, K. (2014). Japan Makes Advance on Stem-Cell Therapy [Online]. Available at: http://online.wsj.com/news/articles/SB10001424127887323689204578571363010820642. Web. 14 Apr. 2015.
 Note: In the United States, some patients have been treated with retina cells derived from embryonic stem cells (ESCs) to treat macular degeneration. There was a successful patient safety test for this stem cell treatment last year that was conducted at the Jules Stein Eye Institute in Los Angeles. The ESC-derived cells used for this study were developed by Advanced Cell Technology, Inc, a company located in Marlborough, Massachusetts.
 Dvorak, K. (2014). Japan Makes Advance on Stem-Cell Therapy [Online]. Available at: http://online.wsj.com/news/articles/SB10001424127887323689204578571363010820642. Web. 8 Apr. 2015.
 Riken.jp. (2014). RIKEN researcher chosen as one of five scientists to watch in 2014 | RIKEN [Online]. Available at: http://www.riken.jp/en/pr/topics/2014/20140107_1/. Web. 14 Apr. 2015.