Studying intractable diseases using iPS cells

抄録

ES and iPS cells belong to pluripotent stem cells that have an ability to differentiate into various cells and undergo sustained growth in vitro. Many studies demonstrated that ES/iPS cells mimic the disease phenotypes in vitro and are powerful tools not only for understanding the molecular mechanisms underlying the pathogenic events but also for developing the new drugs in the future.

Disease-derived iPS cells are generated from somatic cells by over-expressing four reprogramming factors including Oct-3/4, Sox2, Klf4 and cMyc. In particular, the iPS cells are quite useful for studying the intractable diseases as the number of the biopsy samples is limited.

We have generated various kinds of intractable disease-derived iPS cells from the patients' skin fibroblasts and blood cells by Sendai virus (SeV) vector. We concentrated into the study for iPS cells from patients with inherited metabolic diseases such as Niemann-Pick disease type C (NPC). The lipid metabolism was markedly impaired in both the NPC-derived hepatocyte-like and neural cells, resulting in the cholesterol accumulation in both cells. The treatment with Cyclodextrin and its derivatives greatly reduced this accumulation in the patient-derived cells and restored the cellular functions. We are also studying other inherited metabolic diseases. In this symposium, we will present our recent works using the disease-derived iPS cells.