Growth of the iPSC market is supported by an increasing number of clinical studies that are investigating the therapeutic potential of iPSC-derived cell therapy products. Induced pluripotent stem cells (called iPSCs or iPS cells) are a type of stem cell that can become any cell within the human body, giving them enormous potential for use within regenerative medicine.
World’s First iPSC Studies
In 2013, RIKEN launched the world’s first study of an iPSC-derived cell therapy product, treating the first patient in 2014 with iPSC-derived retinal cell sheets.
By 2016, Cynata Therapeutics grabbed the honor of launching the world’s first formal clinical trial of an iPSC-derived cellular product. Using its iPSC-derived mesenchymal stem cell (MSC) product to treat Graft-vs-Host-Disease (GvHD), Cynata treated its first patient in May 2017.
Today, several other studies involving iPSC-derived cellular products are also underway. These include three physician-led studies in Japan, which are are investing the use of iPSC-derived products to treat:
- Heart disease
- Parkinson’s disease
- Aplastic anemia (using iPSC-derived platelets)
Importantly, Fate Therapeutics is now joining the race, positioning itself to launch the first clinical trial of iPSC-derived cellular product within the United States.
Clinical Advances with iPSCs
Clearly, there is accelerating momentum for the clinical applications of induced pluripotent stem cells (iPS cells).
First Investigator Led Clinical Study with iPSCs | Macular Degeneration
In 2013, the first clinical study involving transplant of iPSCs into humans was initiated, with Masayo Takahashi of the RIKEN Center for Developmental Biology in Kobe, Japan investigating the safety of iPSC- derived cell sheets in patients with wet-type age-related macular degeneration.
Unfortunately, this investigator led trial was suspended in 2015 due to safety concerns. As the lab prepared to treat the second trial participant, the team identified two small genetic changes within the patient’s induced pluripotent stem cells and the retinal pigment epithelium (RPE) cells derived from them.
Later, in June 2016 RIKEN Institute resumed the trial using donor-supplied (allogeneic) iPSC-derived cells. According to the Japan Times, this second attempt at the clinical study will use allogeneic rather than autologous iPSC-derived cells, because of cost and time efficiencies.
For this trial, the researchers are creating retinal tissues from iPS cells supplied by Kyoto University’s CiRA, an institution headed by Nobel prize winner Shinya Yamanaka.
First Formal Trial Using iPSCs | Cynata Therapeutics
In a historic event, Cynata Therapeutics received approval in September 2016 to launch the world’s first clinical trial using an iPSC-derived therapeutic product. The trial is using an allogeneic iPSC-derived cell product, called CYP-001.
Cynata’s technology utilized a single one-time blood donation from a single donor to create iPSCs. It then differentiates these iPSCs into mesenchymoangioblast (MCAs), and subsequently, uses this intermediate cell type to create mesenchymal stem cells (MSCs).
Single Blood Donation –> iPSCs –> Mesenchymoangioblast (MCAs) –> MSCs (CYP-001)
Said simply, CYP-001 is an iPSC-derived mesenchymal stem cell product.
Participants in Cynata’s Phase I trial were adults who underwent an allogeneic haematopoietic stem cell transplant (HSCT) and were diagnosed with graft-versus-host disease. (GvHD). The study involves centers in both the UK and Australia.
Physician-lead Trial Using iPSCs for Parkinson’s Disease | Kyoto University
In 2018, Kyoto University announced it will launch a physician-lead trial for Parkinson’s disease. In its July 2018 press announcement, Kyoto University announced that its University Hospital and Center for iPS Cell Research and Application (CiRA) will launch the world’s first clinical trial for Parkinson’s disease to utilize an induced pluripotent stem cell (iPS cell) derived therapeutic product.
For this trial, iPS cells will be used to creates dopaminergic progenitors to be transplanted into human patients.
According to university’s press announcement, the objective of the trial will be to “evaluate the safety and efficacy of transplanting human iPS cell-derived dopaminergic progenitors” into the brains of seven Parkinson’s disease patients.
Physician-lead Trial Using iPSCs for Heart Disease | Osaka University
On 16 May, Nature News 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 team determined that thin sheets of cell grafts can improve heart function. While the treatment will only be tested in three human patients, a follow-up trial could enroll up to ten patients or more.
The Japanese Center for Induced Pluripotent Stem (iPS) Cell Research and Application (CiRA) of Kyoto University is moving iPSC-derived platelets toward clinical trials in humans. Hiroyuki Wadahama, a representative of CiRA, has stated that the center has a goal to conduct a human trial with permission from the Japanese Health Ministry within one year. Of course, this timeline will depend on regulatory approvals, patient recruitment, and safety metrics necessary to conduct the trial.
To produce iPSC-derived platelets, CiRA’s research team is using white blood cells to generate iPSCs and differentiating thesm into megakaryocytes, which are bone marrow cells that manufacture platelets:
White blood cells –> iPSCs –> Megakaryocytes –> Platlets
A major benefit of a platelet-based product is that platelets do not contain nuclei, and therefore, cannot divide or carry genetic information.
NK Cell Cancer Immunotherapy | Fate Therapeutics
In December 2018, the U.S. FDA allowed Fate Therapeutics’ Investigational New Drug (IND) Application for FT500, positioning the company to launch the first clinical trial investigation of an iPSC-derived cell product in the United States. FT500 is a universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master iPSC line.
As stated by Fate Therapeutics, “The Company plans to initiate first-in-human clinical testing of FT500 in combination with checkpoint inhibitor therapy for the treatment of advanced solid tumors.”
Landmark Events for iPSCs
While the past few years have seen many notable achievements related to the commercialization of iPSCs, these clinical events have had particular significant:
- 1st Physician-Led Study of iPSCs for Eye Disease: 2013 was the first year in which iPSC-derived cells were transplanted into humans by Masayo Takahashi of the RIKEN Center in Japan.
- World’s 1st Clinical Trial of an iPSC-Derived Product by Cynata Therapeutics – In May 2017, Cynata Therapeutics treated its first patient with GvHD as part of it phase 1 clinical study of CYP-001 .
- Physician-Led iPSC Study for Parkinson’s Disease – Kyoto University Hospital, in partnership with the CiRA, is transplanting iPSC-derived dopaminergic progenitors into seven patients. The first patient was treated November 2018.
- Physician-Led iPSC Study for Heart Disease – Doctors at Osaka University will be using sheets of tissue derived from iPS cells and grafting them onto diseased human hearts. The trial has received regulatory support, but patient treatment has not yet begun.
- iPSC-derived Platelets – CiRA of Kyoto University is moving iPSC-derived platelets toward clinical trials in humans with the goal to initiate trial activity by 2019.
- FT500 – Fate Therapeutics’ NK cell product derived from a clonal master iPSC line is positioned to be the first trial of iPSC-derived cell product in the U.S.
iPSC Scientific Publications
Furthermore, literature concerning the biology, characteristics, and applications of induced pluripotent stem cells has flourished since iPSCs were first produced in 2006 from mouse cells and in 2007 from human cells. Since 2006, induced pluripotent stem cell publications have risen to a total of 14,290+ publications.
Interest in the therapeutic applications of iPSCs arises from their diverse ability to differentiate into a range of cell types. In addition to the cell therapy applications described above, iPSC research is increasingly focusing on drug development and discovery, toxicological screening, disease modeling, and precision medicine.
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To learn more, view the “Global Induced Pluripotent Stem Cell (iPSC) Industry Report 2018-19.”
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