Abstract
Induced pluripotent stem cells (iPSCs) can proliferate almost indefinitely and differentiate into multiple lineages, giving them wide medical application. As a result, they are being used for new cell-based therapies, disease models and drug development around the world.
In 2014, the world's first clinical study using iPSCs began for the treatment of age-related macular degeneration. iPSCs can be used for regenerative medicine to restore organ function. To push these efforts, we are proceeding with an iPSC stock project in which clinical-grade iPSC clones are being established from “super” donors with homologous HLA haplotypes. Homologous HLA haplotypes are associated with decreased immune response and therefore less risk of transplant rejection. The iPSC stock is being designed with the intention of providing quality-assured cells for medical treatments around the world. In 2015, we started distributing an iPSC stock clone to organizations in Japan.
Other applications of iPSCs include drug screening, toxicity studies and the elucidation of disease mechanisms using disease-specific iPSCs from patients with intractable diseases. iPSCs established from patients contain a complete set of the genes that resulted in the disease and thus represent a new disease model that complements or in some cases replaces animal models.
Finally, accumulating evidence is demonstrating the benefits of iPSCs in drug repositioning. Indeed, Bosutinib, a drug for leukemia was revealed to be efficacious for the treatment of amyotrophic lateral sclerosis (ALS) using a disease model established from patient-derived iPSC. In Addition, we reported a new drug screening system using iPSCs derived from fibrodysplasia ossificans progressiva (FOP) patients, revealing one drug candidate, Rapamycin. Based on these findings, we have received approval from the Japanese government to initiate a clinical trial to treat FOP patients. This clinical trial is the world's first for a drug that is based on results from an iPS cell-based model.
Over the past decade iPSCs research made a great progress. However, there are still various hurdles to be overcome, iPSC-based science is certainly moving forward for delivering innovative therapeutic options to the patients with intractable diseases.
