アクティブボード・２０１２年　７月
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研究発表を行った学会；
・Joint Meeting of JSDB 45th & JSCB 64th
　２０１２年　５月２８日〜３１日（神戸）

タイトル；A high throughput screening system for molecules promoting pancreatic β-cell differentiation of ES cells.

発表者；坂野　大介　氏
　　　（熊本大学　発生医学研究所　多能性幹細胞分野）
Abstract；
The pancreatic transplantation and the pancreatic islet transplant are known as effective treatments for type I diabetes. Donor shortage is an obstacle to the treatment of type I diabetes. Low molecular compounds that promote β-cell differentiation might help us to understand the mechanism of ES cell differentiation into β cells and also contribute to the development of the regenerative medicine. Here, we report the establishment of a high throughput screening system to search for chemical compounds.
We previously reported that embryonic stem (ES) cells cultured on M15 cells (Shiraki et al., 2008), or a synthesized basement membrane (sBM) substratum (Higuchi et al., 2010), efficiently differentiated into an endodermal fate, and then adopted fates of various digestive organs such as the pancreas and liver. This result prompts us to consider three-dimensional scaffolds that resemble the basement membrane to be suitable for the differentiation of ES cells.
To establish a high throughput screening system, we used three-dimensional scaffolds instead of M15 or sBM, and also modified culture media. Using pharmacologically identified bioactive small chemical compounds whose target molecules have been reported, we can estimate the signaling pathway that might be involved.
After induction of pancreatic progenitor, we added chemical compounds for screening. We screened more than 1300 compounds and identified 10 compounds that could increase β-cell number. We classified the hit compounds into several groups according to their target cascades, and found that a higher efficiency of differentiation could be achieved by combining compounds that regulate different target pathways.