Title:
Approach of iPS cells to medical application

Keisuke Okita
Center for iPS Cell Research and Application (CiRA), Kyoto University , Kyoto , Japan

Abstract:
Reprogramming of somatic cells into pluripotent stem cells has been reported by introducing a combination of several factors, Oct3/4, Sox2, Klf4, and c-Myc. The induced pluripotent stem (iPS) cells from patient’s somatic cells would be useful source for drug discovery and cell transplantation therapies. Various methods of iPS cell generation have been developed in order to improvement the efficiency of reprogramming, the quality of iPS cells, and the usability and safety of using iPS cells for clinical applications. The factors that affect the generation of iPS cells can be grouped into four categories; (a) combination of reprogramming factors, (b) transduction method of reprogramming factors, (c) culture conditions and (d) type of original somatic cells. Most human iPS cells were made by retro/leitivirus vectors, which integrate the reprogramming factors into host genomes and may increase tumor formation risk. In fact, activation of c-Myc transgene resulted in tumor formation in mouse model. It is necessary to choose the method best suited for each purpose; basic research or clinical application. We have recently reported the efficient generation of human iPSCs from adult fibroblasts and blood cells using a combination of plasmids. The method should be inspected from a regulative point of view to guarantee their safeness. I’d like to discuss the progress and challenges for the application of iPS cells into clinical field.

References:
An efficient nonviral method to generate integration-free human-induced pluripotent stem cells from cord blood and peripheral blood cells. Stem Cells, 31:458-66 (2013).

Drug screening for ALS using patient-specific induced pluripotent stem cells. Sci Transl Med, 4:145ra104 (2012)

Generation of germline-competent induced pluripotent stem cells. Nature, 448:313-7 (2007)