アクティブボード・２００９年　８月
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研究発表を行った学会；
・42nd Annual Meeting for the Japanese Society of Developmental Biologists.
　２００９年５月２８日〜３１日（新潟）

タイトル；Differentiation of the mouse induced pluripotent stem cells into pancreatic cell lineages.
　
発表者；　山根　恵太郎　氏
　　　（熊本大学　発生医学研究所　多能性幹細胞分野）
Abstract；
Type 1 diabetes is caused by the deficiency of the insulin-producing pancreatic b cells, and it leads to the defection of blood glucose homeostasis. Then, restoration of damaged pancreatic b cells by endocrine pancreas regeneration would be an ideal therapeutic option. Recently, it was demonstrated that the forced expression of transcription factors in the mouse or human somatic cells induced the reprogramming of cell fate and generation of the so-called induced pluripotent stem (iPS) cells (Takahashi. et al., 2006, Nakagawa. et al., 2007). Therefore, iPS cells are expected for their potential use as a surrogate cell source for regenerative medicine.
We previously reported that a mesonephric cell line, M15 cells had the ability to induce the mouse ES cells into pancreatic cell lineages in vitro (Shiraki et al., 2008). Under the optimized condition, 30% of differentiated cells were Pdx1 positive, which is well known to pancreatic progenitor marker. When transplanted under the immunodeficient mouse’s kidney capsule, ES cell-derived Pdx1-expressing cells differentiated into mature pancreatic cell lineages.
Here, we demonstrate that the M15 method can be used for the differentiation of mouse iPS cell line (which was established by Okita & Yamanaka et al., 2007). In the progress of M15 differentiation, iPS cells differentiated into Foxa2/T double positive mesendoderm cells and Foxa2 single positive definitive endoderm cells, sequentially.
And 8 days after differentiation, Pdx1-expressing cells give rise from iPS cells-derived definitive endoderm. We performed transplantation study of iPS cell-derived definitive endoderm cells (which include Pdx1-expressing cells). Four weeks after transplantation, in the recovered graft, insulin ,DBA or somatostatin positive cells were observed.
Previously, we found that ES cells derived definitive endoderm cells could differentiated into insulin positive cells when transplanted under the kidney capsule. Now, we are investigating method of increasing insulin positive cells in vivo by using ES cells and iPS cells.