2019/02/01
Juntendo University Graduate School of Medicine
Keio University School of Medicine
A joint research group, including Project Professor Wado Akamatsu and Researcher Takahiro Shiga from the Center for Genome and Regenerative Medicine at Juntendo University Graduate School of Medicine, and Professor Hideyuki Okano and Project Assistant Professor Koji Nishihara from the Department of Physiology at Keio University School of Medicine, has developed a technology that significantly enhances the differentiation and maturation potential of iPS cells by adding three compounds to the cell culture during the initial establishment phase (reprogramming phase) of the iPS cells.
Because iPS cells can be induced to differentiate into various types of cells, they are applied in fields such as regenerative medicine, therapeutic drug development, and disease mechanism research. However, they require time to mature. Furthermore, because the differentiation and maturation potential varies greatly between cell lines (clones), applying them in regenerative medicine requires pre-selecting clones that can be efficiently induced to differentiate into the target cells, which currently poses a significant burden in terms of time and cost.
In this study, the joint research group discovered that by adding three compounds known as "3i"—the MEK inhibitor (PD184352), the GSK3β inhibitor (CHIR99021), and the FGF receptor inhibitor (SU5402)—to the culture medium during the generation of mouse iPS cells and performing reprogramming for somatic cells to acquire pluripotency: (1) the iPS cells efficiently differentiate in a short period into mature neural stem cells capable of differentiating into glial cells; (2) a trend toward a shorter differentiation induction period is observed in all generated clones; and (3) the generated iPS cells strongly express genes found in the early stages of development. Additionally, it became clear that the culture conditions during the initial phase have a significant impact, as adding 3i after reprogramming does not enhance the differentiation and maturation potential.
It is expected that by applying these results to human iPS cells in the future, this work will contribute significantly to clinical applications in the field of regenerative medicine and to disease research.
The results of this research were published in the online edition of "Stem Cell Reports," the official scientific journal of the International Society for Stem Cell Research (ISSCR), at noon on January 31, 2019 (U.S. Eastern Time).
For the full press release, please see below.