In 2006, Shinya Yamanaka and Kazutoshi Takahashi reported the Nobel Prize winning discovery of induced pluripotent stem cells (iPSCs) in Cell, forever changing the landscape of stem cell research. In the 10 years that have since passed, iPSC technology has advanced the fields of drug discovery, toxicology, disease modelling, and cellular medicine.
To celebrate and honor these achievements, this article highlights the the most epic iPSC advances of all time.
10 Epic iPS Cell Advances
1. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors (Aug 25, 2006)
Clearly, the winner for this list is Takahashi and Yamanaka’s original paper about producing iPS cells in mice.
As stated in the Abstract, “Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions.”
2. CiRA and Takeda Enter 10-year Collaboration on iPS Cell Research (April 7, 2015)
Any iPS cell announcement spanning 10 years and investing 20 billion yen is worthy of this list. Is is also noteworthy to get extensive funding support from Japan’s largest pharmaceutical company (Takeda).
As stated in the announcement, the “Center for iPS Cell Research Application (CiRA) of Kyoto University and Takeda Pharmaceutical Company Limited (Takeda) announced today that they will work together to develop clinical applications of induced pluripotent stem cells in areas such as heart failure, diabetes mellitus, neurological disorders and cancer immunotherapy. This collaboration is aligned with the purpose of National Projects of Japan on clinical applications of iPS cell technologies. Takeda will provide research facilities at its Shonan Research Center and collaborative funding of 20 billion yen over a 10-year period. In addition, Takeda will provide more than 12 billion yen worth of research support.”
3. Japanese woman is first recipient of next-generation stem cells (Sept 12, 2014)
Without a doubt, the first use ever of iPSC-derived cells within a human being was a major medical breakthrough.
As stated in the release, “A Japanese woman in her 70s is the first person to receive tissue derived from induced pluripotent stem cells, a technology that has created great expectations since it could offer the same regenerative potential as embryo-derived cells but without some of the ethical and safety concerns. In a two-hour procedure, a team of three eye specialists lead by Yasuo Kurimoto of the Kobe City Medical Center General Hospital implanted a 1.3 by 3.0 millimetre sheet of retinal pigment epithelium cells into an eye of the Hyogo prefecture resident, who suffers from age-related macular degeneration, a common eye condition that can lead to blindness.”
4. Fujifilm Holdings to Acquire Cellular Dynamics International, Inc. (March 30, 2015)
This was a massive announcement within the iPS cell community, because it was the first (and so far only) time an iPS cell company has been acquired by a large multinational company for hundreds of millions of dollars.
As stated in the company press release, “FUJIFILM Holdings Corporation (“Fujifilm”) and Cellular Dynamics International, Inc. (“CDI”), a leading developer and manufacturer of fully functioning human cells in industrial quantities to precise specifications, today announced that the two companies have entered into a definitive agreement whereby Fujifilm will acquire CDI via an all-cash tender offer to be followed by a second step merger. Fujifilm aims to acquire all issued and outstanding shares of CDI’s common stock for $ 16.5 per share or approximately $ 307 million (on a fully diluted basis).
5. Cynata Approved to Launch World’s 1st Clinical Trial with an Allogeneic iPSC-Derived Product (Sept 20, 2016)
This announcement makes the list, because Cynata Therapeutics is launching the world’s first clinical trial to involve a therapeutic product derived from allogeneic iPS cells.
Specifically, Australian stem cell company Cynata Therapeutics (ASX:CYP) announced that it has received advice from the UK Medicines and Healthcare products Regulatory Agency (MHRA) that its Phase I clinical trial application has been approved. The primary objective of the trial is to assess safety and tolerability, while the secondary objective is to evaluate the efficacy of two infusions of CYP-001 in adults with steroid-resistant GvHD. Cynata’s CYP-001 is an iPSC-derived mesenchymal stem cell (MSC) product generated from iPS cells provided by a single donor a single time.
6. A new Parkinson’s disease treatment by 2018: transplantation of nerve cells produced by induced pluripotent stem cells (iPS cells) Prof. Jun Takahashi, Kyoto University (Aug 15, 2014)
It is revolutionary to announce that an iPS cell therapy is being developed for treatment for Parkinson’s disease (PD), because Parkinson’s disease is a chronic and progressive movement disorder within no known cure.
As stated in the announcement, “On August 15, 2014, Prof. Jun Takahashi, at the Center for iPS Cell Research and Application of Kyoto University, announced that he will start medical treatment for Parkinson’s disease at medical institutions using induced pluripotent stem cells (iPS cells) by 2018. For this treatment, iPS cells are generated from a patient’s own cells and then differentiated into nerve cells. These are then transplanted into a patient’s brain after their safety has been assured. Clinical research for this treatment will begin in January 2015. Research in the use of cells from another person is going to start by 2018.”
7. Cellular Dynamics Announces Partnership with The Michael J. Fox Foundation for Parkinson’s Research to Provide Resources for Developing New Therapies (May 25, 2016)
This announcement made the list, because it is the first prominent example of a major market player establishing a powerful collaboration with a stem cell advocacy group.
As stated in the company press release, “Cellular Dynamics International, Inc. (CDI), a FUJIFILM company, today announced an agreement with The Michael J. Fox Foundation for Parkinson’s Research (MJFF) to derive induced pluripotent stem cells (iPSCs) from 85 people in the MJFF-sponsored Parkinson’s Progression Markers Initiative (PPMI). The collaborators will provide the cells to the scientific community in concert with rich available clinical and imaging data on these study volunteers in service to their shared goal to provide resources to accelerate the development of new therapies.”
8. Kyoto University Hospital to open iPS cell therapy center in 2019 (Feb 24, 2015)
This announcement is a bold and courageous step toward introducing iPS cell therapies into clinical practice.
As stated in the release, “Kyoto University Hospital says it will open a center to conduct clinical studies on induced pluripotent stem cell therapies in 2019 year. Officials said the 30-bed ward will test the efficacy and safety of the therapies on volunteer patients. The hospital aims to break ground at the site next February and complete construction by September 2019.”
While the world’s first clinical trial involving transplant of iPSCs into humans run by Masayo Takahashi was put on hold due to safety concerns, the Riken recently stated that it will resume a clinical study in cooperation with Kyoto University and other medical institutes.
According to this announcement by the Japan Times, this attempt at a clinical study will involve allogeneic rather than autologous iPSC-derived cells for purposes of cost and time efficiency. The researchers will be developing retinal tissues from iPS cells supplied by Kyoto University’s Center for iPS Cell Research and Application, headed by Nobel laureate Shinya Yamanaka. Currently, it is the world’s only clinical trial anticipated to involve an allogeneic iPS cell product, other than Cynata Therapeutics upcoming clinical trial for CYP-001, an allogeneic iPSC-derived mesenchymal stem cell (MSC) product that will be tested for GvHD.
10. Cellular Dynamics Announces Launch of World’s Largest Public Stem Cell Bank and the Availability of the First 300 iPSC Lines (Sept 1, 2015)
This announcement is significant, because it announces the launch of the world’s largest public iPS cell bank. It also represents support for the concept of a global iPS cell bank capable of providing healthy and diseased cell lines to researchers worldwide.
As stated in the release, “Cellular Dynamics International, Inc. (CDI), a FUJIFILM company, today announced the launch of the world’s largest publicly available stem cell bank, the California Institute for Regenerative Medicine (CIRM) hPSC Repository, and the availability of the first 300 induced pluripotent stem cell (iPSC) lines in September. These high quality, disease-specific iPSC resources are now accessible to academic and industry researchers for disease modeling, target discovery and drug discovery. In 2013, CIRM awarded CDI $16 million to create induced pluripotent stem cell (iPSC) lines for each of 3,000 healthy and diseased volunteer donors across 11 common diseases and disorders to be made available through the CIRM hPSC Repository.”
Would you add any new iPSC announcements to this list? Leave your suggestions in the comments below.