Small Molecules that Promote Self-Renewal of Stem Cells and Somatic Cell Reprogramming

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.