Recent years have seen major advances in the clinical applications of iPSCs, with Cynata Therapeutics progressing the world’s first formal trial of an iPSC-derived cell therapeutic and demonstrating that CYP-001, its lead iPSC-derived mesenchymal stem cell (MSC) product candidate, met all safety and efficacy endpoints in its Phase 1 trial for GvHD.
With multiple physician-led iPSC studies also underway in Japan for applications ranging from Parkinson’s disease to heart disease, the iPSC market is poised to for burgeoning growth. There has also been dramatic progress with production and differentiation technologies related to iPSCs, as well as growing use of iPSCs within drug discovery, disease modelling, tissue engineering, and precision medicine.
Introduction to the iPSC Market
Groundbreaking experimentation in 2006 led to the introduction of induced pluripotent stem cells (iPSCs). These are adult cells which are isolated and then transformed into embryonic-like stem cells through the manipulation of gene expression, as well as other methods. Research and experimentation using mouse cells by Shinya Yamanaka’s lab at Kyoto University in Japan was the first instance in which there was a successful generation of iPSCs.
In 2007, a series of follow-up experiments were done at Kyoto University in which human adult cells were transformed into iPSCs. Nearly simultaneously, a research group led by James Thomson at the University of Wisconsin-Madison accomplished the same feat of deriving iPSC lines from human somatic cells.
Since the discovery of iPSCs a large and thriving research product market has grown into existence, largely because the cells are non-controversial and can be generated directly from adult cells. While it is clear that iPSCs represent a lucrative product market, methods for commercializing this cell type are still being explored, as clinical studies investigating iPSCs continue to increase in number.
iPS Cell Therapies
2013 was a landmark year in Japan because it saw the first cellular therapy involving the 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 was investigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration.
Although the study was suspended in 2015 due to safety concerns, in June 2016 RIKEN Institute announced that it would resume the clinical study using allogeneic rather than autologous iPSC-derived cells, because of the cost and time efficiencies.
In a world-first, Cynata Therapeutics received approval in September 2016 to launch the world’s first formal clinical trial of an allogeneic iPSC-derived cell product, called “CYP-001.” The study involves centers in the UK and Australia. In this trial, Cynata is testing an iPS cell-derived mesenchymal stem cell (MSC) product for the treatment of GvHD.
On 16 May 2018, Nature News then reported that “Japan’s health ministry gave doctors at Osaka University permission to take sheets of tissue derived from iPS cells and graft them onto diseased human hearts.” The team of Japanese doctors, led by cardiac surgeon Yoshiki Sawa at Osaka University, will use iPS cells to “create a sheet of 100 million heart-muscle cells.” From preclinical studies in pigs, the medical team determined that thin sheets of cell grafts can improve heart function, likely through paracrine signaling.
Kyoto University Hospital in Kobe, Japan also stated it would be opening an iPSC therapy center in 2019, for purposes of conducting clinical studies on iPS cell therapies. Officials for Kyoto Hospital said it will open a 30-bed ward to test the efficacy and safety of the therapies on volunteer patients, with the hospital aiming to initiate construction at the site in February of 2016 and complete construction by September 2019.
iPS Cell Market Competitors
In 2009 ReproCELL, a company established as a venture company originating from the University of Tokyo and Kyoto University was the first to make iPSC products commercially available with the launch of its human iPSC-derived cardiomyocytes, which it called “ReproCario.”
Cellular Dynamics International, a Fujifilm company, is another major market player in the iPSC sector. Similar to ReproCELL, CDI established its control of the iPSC industry after being founded in 2004 by Dr. James Thomson at the University of Wisconsin-Madison, who in 2007 derived iPSC lines from human somatic cells for the first time ever (the feat was accomplished simultaneously by Dr. Shinya Yamanaka’s lab in Japan).
A European leader within the iPSC market is Ncardia, formed through the merger of Axiogenesis and Pluriomics. Founded in 2001 and headquartered in Cologne, Germany, Axiogenesis initially focused on generating mouse embryonic stem cell-derived cells and assays. After Yamanaka’s groundbreaking iPSC technology became available, Axiogenesis was the first European company to license and adopt Yamanaka’s iPSC technology in 2010.
Ncardia’s focus lies on preclinical drug discovery and drug safety through the development of functional assays using human neuronal and cardiac cells, although it is expanding into new areas. Its flagship offering is its Cor.4U human cardiomyocyte product family, including cardiac fibroblasts.
Dozens of iPSC banks have also emerged to meet the rising demand among scientists for disease-specific research grade iPSC lines and services. A leader in this area is the European Bank for induced pluripotent Stem Cells (EBiSC) in UK. Another market competitor is ORIG3N in Boston, MA, who is creating the world’s largest blood cell repository and using these cells to produce patient-specific iPSCs.
In summary, market leaders have emerged in all areas of iPSC development, including:
- Drug Development and Discovery: CDI, a Fujifilm Company, in Madison, Wisconsin; Ncardia in Cologne, Germany
- Cellular Therapy: RIKEN Center, in Kobe, Japan; Kyoto University in Kyoto, Japan; Cynata Therapeutics in Australia
- iPSC Banking: European Bank for induced pluripotent Stem Cells (EBiSC) in UK; ORIG3N in Boston, Massachusetts
- iPSC Research Products: CDI, a Fujifilm Company; Ncardia, ReproCELL; Thermo Fisher Scientific; STEMCELL Technologies; BD Biosciences; Axol Bioscience; and many more
iPS Cell Commercialization
There are also four major areas of commercialization for induced pluripotent stem cells, as described below:
- Drug Development and Discovery: iPSCs have the potential to transform drug discovery by providing physiologically relevant cells for compound identification, target validation, compound screening, and tool discovery.
- Cellular Therapy: iPSCs are being explored in cellular therapy applications for purposes of reversing injury or disease.
- Toxicology Screening: iPSCs can be used for toxicology screening, which is the use of stem cells or their derivatives (tissue-specific cells) to assess the safety of compounds or drugs within living cells.
- iPSC Banks: iPSC banks provide researchers with the opportunity to investigate a diverse range of conditions using iPSC-derived cell types produced from both healthy and diseased donors.
The Future of iPS Cells
In summary, iPSCs represent a promising tool for use in the reversal and repair of many previously incurable diseases.
To profit from this lucrative and rapidly expanding market, you need to understand your key strengths relative to the competition, intelligently position your products to fill gaps in the market place, and take advantage of crucial iPSC trends.