The ground state of embryonic stem cells (ESCs) is closely related to the development of regenerative medicine. Particularly, long-term culture of ESCs in vitro, maintenance of their undifferentiated state, self-renewal and multi-directional differentiation ability is the premise of ESCs mechanism and application research. Induced pluripotent stem cells (iPSC) reprogrammed from mouse embryonic fibroblasts (MEF) cells into cells with most of the ESC characteristics show promise towards solving ethical problems currently facing stem cell research. However, integration into chromosomal DNA through viral-mediated genes may activate proto oncogenes and lead to risk of cancer of iPSC. At the same time, iPS induction efficiency needs to be further improved to reduce the use of transcription factors. In this review, we discuss small molecules that promote self-renewal and reprogramming, including growth factor receptor inhibitors, GSK-3β and histone deacetylase inhibitors, metabolic regulators, pathway modulators as well as EMT/MET regulation inhibitors to enhance maintenance of ESCs and enable reprogramming. Additionally, we summarize the mechanism of action of small molecules on ESC self-renewal and iPSC reprogramming. Finally, we will report on the progress in identification of novel and potentially effective agents as well as selected strategies that show promise in regenerative medicine. On this basis, development of more small molecule combinations and efficient induction of chemically induced pluripotent stem cell (CiPSC) is vital for stem cell therapy. This will significantly improve research in pathogenesis, individualized drug screening, stem cell transplantation, tissue engineering and many other aspects.

中文翻译：

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促进干细胞自我更新和体细胞重编程的小分子。

胚胎干细胞（ESC）的基态与再生医学的发展密切相关。特别地，ESCs的长期培养，维持其未分化状态，自我更新和多向分化能力是ESCs机理和应用研究的前提。从小鼠胚胎成纤维细胞（MEF）细胞重编程为具有大多数ESC特性的细胞的诱导性多能干细胞（iPSC）显示出有望解决目前干细胞研究面临的伦理问题。但是，通过病毒介导的基因整合入染色体DNA可能会激活原癌基因，并导致患iPSC的风险。同时，iPS诱导效率需要进一步提高以减少转录因子的使用。在这篇评论中 我们讨论促进自我更新和重编程的小分子，包括生长因子受体抑制剂，GSK-3β和组蛋白脱乙酰基酶抑制剂，代谢调节剂，途径调节剂以及EMT / MET调节抑制剂，以增强ESC的维持并实现重编程。此外，我们总结了小分子对ESC自我更新和iPSC重新编程的作用机制。最后，我们将报告鉴定新型和潜在有效药物以及在再生医学中显示出希望的选定策略的进展。在此基础上，开发更多的小分子组合并有效诱导化学诱导的多能干细胞（CiPSC）对于干细胞治疗至关重要。这将大大改善有关发病机理，个体化药物筛选，