Developing induced pluripotent stem cell (iPSC) products requires a thorough understanding of the evolution of iPSC research advances. Because the cell type was recently discovered in 2006, the following presents a decade-long timeline of key events in the discovery and evolution of induced pluripotent stem cell products.
The research events below drove forward interest in the use of iPSCs for basic research and clinical applications. These events are the reason that the first clinical trial involving the implantation of iPSCs into humans was initiated in 2013, to assess the capacity of the cell type to treat loss of eyesight due to macular degeneration.
For this reason, stem cell company executives and stem cell industry investors will be better suited to make future decisions about iPSC products if they have a historical understanding of the recent past and the rate at which research advances with the cell type accelerated.
Rate of iPSC Research Product Advances
Interestingly, the rate of iPSC research advances was most rapid from 2008 to 2009, a period shortly (but not immediately) after iPSCs were discovered in 2006. However, the period from 2013 to present has been the first period during which iPSCs have been investigated in clinical settings, and this trend is expected to continue as Kyoto University Hospital in Kobe, Japan, has announced that it will be opening an iPSC therapy center in 2019, for purposes of conducting clinical studies on iPSC therapies.
A full timeline of key events in the discovery and evolution of induced pluripotent stem cell products is shown below:
Timeline of Events in the Discovery and Evolution of iPSC Products
DATE |
DESCRIPTION OF EVENT |
| August 2006 | Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures achieved using defined factors. |
| June 2007 | Developmental reprogramming after chromosome transfer into mitotic mouse zygotes is achieved. |
| December 2007 | Induced pluripotent stem cell lines are derived from human somatic cells. (The accomplishment is achieved nearly simultaneously by research groups led by Shinya Yamanaka and James Thomson.) |
| June 2008 | A combined chemical and genetic approach for the generation of induced pluripotent stem cells is announced. |
| July 2008 | Direct reprogramming through integrative genomic analysis is achieved. |
| August 2008 | Induced pluripotent stem cells generated from patients with ALS are differentiated into motor neurons. |
| September 2008 | Disease-specific induced pluripotent stem cells are generated. |
| September 2008 | Hetero karyon–based reprogramming of human B lymphocytes for pluripotency is shown to require Oct4 but not Sox2. |
| November 2008 | Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes is achieved. |
| November 2008 | Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2 is achieved. |
| November 2008 | Generation of mouse induced pluripotent stem cells without viral vectors is achieved. |
| November 2008 | Induction of pluripotent stem cells from mouse embryonic fibroblasts by Act4 and Klf4 with small-molecule compounds is reported. |
| November 2008 | Two supporting factors greatly improve the efficiency of human iPSC generation. |
| December 2008 | Guidelines and techniques for the generation of induced pluripotent stem cells are published. |
| December 2008 | Generation of induced pluripotent stem cells from adult rhesus monkey fibroblasts is achieved. |
| January 2009 | Generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy is reported. |
| March 2009 | Parkinson’s Disease patient-derived induced pluripotent stem cells free of viral reprogramming factors are generated. |
| April 2009 | Virus-free induction of pluripotent stem cells is achieved. |
| April 2009 | Directed differentiation of human-iPSCs generates active motor neurons. |
| May 2009 | Induced pluripotent stem cells using recombinant proteins are generated. |
| June 2009 | Human-induced pluripotent stem cells by direct delivery of reprogramming proteins are generated. |
| June 2009 | Micro RNA profiling of human-induced pluripotent stem cells occurs. |
| June 2009 | Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and a tool for prenatal diagnosis for genetic diseases. |
| June 2009 | Mouse-induced pluripotent stem cells by transient expression of a single non-viral polycistronic vector are generated. |
| July 2009 | Disease-corrected haematopoietic progenitors from Fanconi anaemia iPSCs are generated. |
| August 2009 | Immortalization eliminates a roadblock during cellular reprogramming into iPSCs. |
| September 2009 | IPSCs produce viable mice through tetraploid complementation. |
| September 2009 | Adult mice generated from iPSCs. |
| October 2009 | Generation of pig iPSCs with a drug-inducible system is achieved. |
| February 2010 | Generation of iPSCs from adult mouse adipose tissue-derived and neural stem cells is made more efficient. |
| October 2010 | A potential role for insulin-like growth factors signaling is identified in the iPSC formation. |
| October 2011 | Generation of iPSCs by nuclear reprogramming is achieved. |
| October 2012 | The Nobel Prize in Physiology or Medicine 2012 is awarded jointly to John Gurdon & Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. |
| January 2013 | Cellular Dynamics announces an agreement with the pharmaceutical giant AstraZeneca for use of iPSC-derived human cells in drug discovery research. |
| June 2013 | A team from National Taiwan University (NTU) produces the world’s first iPSCs for Pompe disease, a rare metabolic disorder caused by maltase deficiency. Pompe disease-iPSCs reproduce both the cell phenotype and pathological features of Pompe disease. |
| August 2013 | The first clinical study involving transplant of iPSCs into humans began to investigate the use of iPSCs in treating patients with macular degeneration. This clinical study is now underway at the Riken Center in Japan, led by Masayo Takahashi. |
| January 2014 | Masayo Takahashi of the RIKEN Center for Developmental Biology in Kobe, Japan, is chosen by the journal Nature as one of five scientists to watch in 2014. She is heading the world’s first clinical research involving transplant of iPSCs into humans, by investigating the safety of iPSC- derived cell sheets in patients with wet-type age-related macular degeneration. |
| March 2015 | Kyoto University Hospital in Kobe, Japan announces that it will be opening an iPSC therapy center in 2019, for purposes of conducting clinical studies on iPSC therapies. |
| June 2015 | First autologous iPSC transplant into a human eye (Riken, Japan) completes initial safety phase for macular degeneration. |
| August 2021 |
Fate Therapeutics’ FT819, an off‑the‑shelf, iPSC‑derived CAR‑T cell therapy, entered a Phase 1 clinical trial and treated its first patient in that study. This program is widely cited as the first iPSC‑derived T‑cell therapy to enter clinical investigation. |
| February 2023 |
A Phase 1/2 study (LAPiS) dosed its first patient with an iPSC‑derived cardiomyocyte therapy (HS‑001) for advanced heart failure, a trial is conducted in Japan/Denmark. The treatment involves iPSC‑derived heart muscle cells and is injected during surgery. |
| November 2024 |
Cellistic announced that its dedicated iPSC manufacturing facility received GMP certification from the Belgian Federal Agency for Medicines and Health Products, making it qualified for regulated production of iPSC-based therapies. |
| Q1/Q2 2025 |
BlueRock Therapeutics (Bayer) announced it would be advancing an iPSC-derived Parkinson’s therapy (bemdaneprocel) into a Phase III trial, expected to start in first half of 2025. |
| July 2025 |
I Peace, Inc. (a GMP CDMO) announced a collaboration with Vita Therapeutics to jointly develop hypoimmune (universal) iPSCs for cell transplantation therapy (initially for FSHD), with the resulting master cell banks planned for FDA regulatory use. |
| February 2026 |
The world witnessed the approval of the world’s first two iPSC-derived medicines, as Japan’s health ministry panel authorized their commercialization on February 19, 2026. The approved therapies are ReHeart, developed by Cuorips Inc., a regenerative medicine company spun out of research at Osaka University, and Amchepry, developed by Sumitomo Pharma Co., Ltd. in collaboration with Racthera Inc. ReHeart is for the treatment of severe heart failure and Amchepry is for the treatment of patients with Parkinson’s disease. |
