Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Departments of Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Stem Cell Rev Rep. 2020 Jun;16(3):511-523. doi: 10.1007/s12015-020-09965-w.
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.
胚胎干细胞（ESCs）的基础状态与再生医学的发展密切相关。特别是，ESCs 的长期体外培养、维持其未分化状态、自我更新和多向分化能力是 ESCs 机制和应用研究的前提。从小鼠胚胎成纤维细胞（MEF）细胞重编程而来的诱导多能干细胞（iPSC）表现出具有 ESC 大部分特性的细胞特征，有望解决当前干细胞研究面临的伦理问题。然而，通过病毒介导的基因整合到染色体 DNA 中可能会激活原癌基因，导致 iPSC 癌症风险。同时，iPS 诱导效率需要进一步提高，以减少转录因子的使用。在这篇综述中，我们讨论了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 和组蛋白去乙酰化酶抑制剂、代谢调节剂、通路调节剂以及 EMT/MET 调节抑制剂，以增强 ESCs 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 重编程的作用机制。最后，我们将报告鉴定新型潜在有效药物的进展以及在再生医学中显示出前景的选定策略。在此基础上，开发更多的小分子组合和有效的化学诱导多能干细胞（CiPSC）诱导对于干细胞治疗至关重要。这将极大地改善发病机制、个体化药物筛选、干细胞移植、组织工程等多个方面的研究。
