Induced pluripotent stem cells (iPSCs) were originally generated from mouse and human skin fibroblasts by introducing four identified transcription factor genes. As iPSCs have the ability to proliferate almost indefinitely and differentiate into multiple lineages, there are great hopes for medical and pharmaceutical applications. Many improvements have been achieved in iPSC production in both safety and efficacy.
iPSCs can be generated from various genetically identified individuals including patients. These iPSCs and subsequently differentiated target cells/ tissues would provide unprecedented opportunities in regenerative medicine, disease modelling, proof-of-concept studies in drug development, drug screening, and future personalized medicine.

SIR2 and related genes (sirtuins) are NAD-dependent deacetylases that link metabolism, protein acetylation and aging in a variety of species. Sirtuins are involved in the longevity conferred calorie restriction (CR). The mammalian sirtuins SIRT1-7 are involved in changes in stress resistance and metabolism that are triggered by CR, which not only extends life span, but also protects against many diseases of aging. In this talk, I will discuss new findings in the lab regarding SIRT1 and NAD+. I will also discuss the role of SIRT1 in adult stem cells. Our findings place sirtuins at the center of metabolism and health.

We have started clinical research using iPS cells for Age-related macular degeneration (AMD). Now we are preparing the first patinet’s iPSC-derived RPE (hiPSC-RPE) cell sheets optimized to meet clinical requirements including quality, quantity, consistency, and safety. We also evaluate the photoreceptor transplantation using iPS-derived 3D retinal induction methods. We observed survival of photoreceptor cells with outer segments for more than 6 months.
Thus, iPS cell-derived retinal cell transplantation is promising. However, the effect of the treatments will be limited for the first decade. We should know precisely about the possibility and the limitation of the therapy.

Discovery of CFH and ARMS2 as susceptibility genes of age-related macular degeneration (AMD) established the importance of genetic polymorphisms in the development of AMD and now more than 10 genes are known to be associated with AMD. On the other hand, only few studies are available to show a positive contribution of gene polymorphisms to clinical phenotypes of AMD. Most of the studies showing such negative contribution focus on disease-susceptibility genes and rather limited information on phenotypes is used. However, our recent genome-wide association study revealed that ARMS2 is a strong predictor of AMD prognosis. Furthermore, we found that MMP20 is associated with the lesion size but not with the onset of AMD, which suggests MMP20 would be a novel target for the treatment of AMD. So, gene polymorphisms are important not only for the development of AMD but also play an important role in determining phenotypes of the disease. Further studies are needed to make treatment of AMD more personalized and change our patient care.