NOVEL LOW-MOLECULE COMPOUND FOR PROMOTING PLURIPOTENT STEM CELL GENERATION, MAINTENANCE, AND PROLIFERATION, AND COMPOSITION AND CULTURING METHOD CONTAINING SAME
申请人:Korea Research Institute of Bioscience
and Biotechology
公开号:EP2774918A1
公开(公告)日:2014-09-10
According to the present invention, when the novel low-molecular-weight compound RSC-133 is added in a culture process for producing reprogrammed pluripotent stem cells from human differentiated cells, it can increase the efficiency of reprogramming and can significantly reduce the time required for the induction of reprogramming. Particularly, the novel compound RSC-133 can substitute for c-Myc acting as both a reprogramming factor and an oncogenic factor, and it can effectively increase the efficiency of reprogramming in both normal oxygen culture conditions and hypoxic culture conditions. In addition, RSC-133 can inhibit the induction of aging occurring in the reprogramming process, exhibits the effect of promoting cell proliferation, and induces epigenetic activation to improve culture conditions for induction of reprogramming. The present invention will contribute to optimizing a process of producing induced pluripotent stem cells from a small amount of patient-specific somatic cells obtained from various sources, and thus it will significantly improve a process of developing clinically applicable personalized stem cell therapy agents and new drugs and will facilitate the practical use of these agents and drugs. In addition, the novel low-molecular-weight compound RSC-133 can provide a cell culture medium effective for maintaining the undifferentiated state of human embryonic stem cells that are typical pluripotent stem cells. The medium composition containing RSC-133 can effectively induce the proliferation of human embryonic stem cells in an undifferentiated state and can be effectively used for the development of a system for culturing large amounts of embryonic stem cells.
根据本发明,当新型低分子量化合物RSC-133被添加到从人类分化细胞生产重编程多能干细胞的培养过程中时,它可以提高重编程的效率,并能显著缩短诱导重编程所需的时间。特别是,新型化合物 RSC-133 可替代 c-Myc 同时作为重编程因子和致癌因子,在正常氧培养条件和低氧培养条件下都能有效提高重编程效率。此外,RSC-133 还能抑制重编程过程中出现的老化诱导,具有促进细胞增殖的作用,并能诱导表观遗传活化,改善诱导重编程的培养条件。本发明将有助于优化从各种来源获得的少量患者特异性体细胞中生产诱导多能干细胞的过程,从而显著改善临床适用的个性化干细胞治疗药物和新药的开发过程,并促进这些药物和新药的实际应用。此外,新型低分子量化合物 RSC-133 还能提供一种细胞培养基,有效维持作为典型多能干细胞的人类胚胎干细胞的未分化状态。含有 RSC-133 的培养基组合物能有效诱导处于未分化状态的人类胚胎干细胞增殖,可有效用于开发培养大量胚胎干细胞的系统。