Generation of Pluripotent Stem Cells for Clinical Application

Shinya Yamanaka (Director, Center for iPS Cell Research and Application, Kyoto University)

Research Area: Translational Research for Intractable Immune Disorders and Infectious Diseases (FY2003-2008)
Succeeded in generating human induced pluripotent stem (iPS) cells
Pioneering the possibility of rejection-free graft treatment for various refractory diseases

Research Overview
Embryonic stem (ES) cells which are made from fertilized eggs proliferate rapidly while maintaining pluripotency. These properties make such cells attractive as tools in regenerative medicine. However, the use of ES cells presents some problems, including ethical issues arising from the need to destroy human embryos, and rejection after transplantation. To solve these problems, there is urgent demand for techniques to generate pluripotent stem cells derived from patients themselves.
Prof. Yamanaka successfully generated iPS cells with gene expression patterns as well as form and proliferative capacity similar to those of human ES cells by transfecting adult human fibroblasts with four transcription factors using retroviral vectors and by culturing the cells. The human iPS cells generated exhibited the ability to differentiate into various cells, such as nerve / myocardial / cartilage / fat intestine-like endodermal cells. Subsequently, he also successfully generated iPS cells using three of the four factors (due to concern that one of the four might facilitate tumor formation) and plasmid without retroviruses (as the retroviruses initially used also had the potential to cause tumor formation), thereby developing a series of safe, promising iPS-cell creation techniques for clinical application.

Impact of Research Achievements
The creation of iPS cells from the somatic cells of patients with intractable diseases and their differentiation into therapeutic cells are expected to lead to cell transplantation therapies that are free of ethical problems and host rejection issues.
For example, there are over 50 thousand patients with spinal cord damage. In 2008, heart disease was the second most common cause of death in Japan (approx. 180,000).
■ Neurons, Cardiac myocytes and hepatocytes induced from iPS cells greatly contribute to the search for safe, effective drugs.
■ Potential market in the field of regenerative medicine in 2030 estimated to be about 330 billion yen in Japan only. Potential global market estimated to be 10 trillion yen.

* The method has since been improved rapidly by Prof. Yamanaka and his colleagues; it now requires fewer factors and uses plasmid without retroviruses.