Establishment of Myocardial Regeneration Therapy Using Small Molecule-Responsive Artificial Receptors For Growth Factor Signal Transduction

来自Wnt配体或粒细胞集落刺激因子（G-CSF）的信号转导与参与心肌细胞分化或来自外部应激刺激的细胞存活的途径有关。控制多能干细胞中的这些信号有望提高植入后细胞存活以及心肌细胞诱导的效率。然后，我们试图在Wnt 3a或G-CSF不存在的情况下产生可以激活信号通路的小分子响应性人工受体。在本研究项目中，我们构建了嵌合受体，其中抗荧光素（FL）抗体的单链Fv连接到Wnt 3a或G-CSF受体的跨膜/胞质结构域。用这些嵌合受体转导的小鼠ES细胞或iPS细胞能够激活响应于FL缀合的BSA（BSA-FL）作为同源配体的信号，并且当用BSA-FL刺激时，显示出增加的心肌细胞分化效率。

Signal transduction from Wnt ligands or Granulocyte Colony Stimulating factor (G-CSF) links to pathways involved in myocardial cell differentiation or cell survival from external stress stimuli. To control these signals in pluripotent stem cells is expected to improve the efficiency for cell survival after implantation as well as for myocardial cell induction. Then, we attempted to generate small molecule-responsive artificial receptors that can activate signal pathways, in the absence of Wnt3a or G-CSF. In the present research project, we constructed chimeric receptors in which single-chain Fv of anti-fluorescein (FL) antibody was tethered to transmembrane/cytoplasmic domains of the receptor for Wnt3a or G-CSF. Mouse ES cells or iPS cells transduced with these chimeric receptors are able to activate the signals in response to FL-conjugated BSA (BSA-FL) as a cognate ligand, and show increased efficiency for myocardial cell differentiation when they are stimulated with BSA-FL.