October 27, 2017
Keio University School of Medicine
Juntendo University Graduate School of Medicine
Japan Agency for Medical Research and Development (AMED)
A joint research team led by Professor Hideyuki Okano of the Department of Physiology, Keio University School of Medicine, and Project Professor Wado Akamatsu of the Center for Genomic and Regenerative Medicine, Juntendo University Graduate School of Medicine, has developed a fundamental technology to promote the differentiation potential of human pluripotent stem cells by adding three small molecule compounds.
Pluripotent stem cells (ES cells and iPS cells) are cell lines capable of differentiating into any tissue or cell in the body, and are expected to have a wide range of applications, including regenerative medicine. However, human pluripotent stem cells, particularly iPS cells, have properties such as 1) variations in differentiation efficiency among cell lines and 2) a relatively slow differentiation speed. This has created a problem: it is necessary to pre-select pluripotent stem cell lines that are prone to differentiate into the desired cells and tissues, and even when using selected cell lines, achieving highly efficient differentiation induction requires significant effort and a long period of time.
The joint research team has now discovered that by adding three compounds—SB431542, Dorsomorphin, and CHIR99021—to the culture medium of cell lines for five days, human pluripotent stem cells can be induced into a state of enhanced planar differentiation in a very short period. They defined the state induced by these three small molecule compounds as "CTraS" and found that cells that underwent CTraS induction showed a significant increase in both the efficiency and speed of differentiation into target cells, allowing for the rapid replication of disease phenotypes in disease models. Furthermore, CTraS enables even cell lines that are difficult to differentiate into specific cells to differentiate into the target cells (in this study, neurons) with high efficiency. This eliminates the need to select cell lines that are prone to differentiate into the desired cells, thereby greatly improving research efficiency.
Since the CTraS-mediated promotion of differentiation developed in this study is applicable to diverse cell lineages, it is expected to contribute to all applied technologies using human pluripotent stem cells and, in particular, to become a foundation that will accelerate regenerative medicine, disease research, and drug development.
The results of this research were published in the online edition of *Stem Cell Reports*, the official journal of the International Society for Stem Cell Research (ISSCR), at noon on October 26, 2017 (U.S. Eastern Time).
For the full press release, please see below.