Chemical transdifferentiation is a technique that utilizes small molecules to directly convert one cell type into another without passing through an intermediate stem cell state. This technique offers several advantages over other methods of cell reprogramming, such as simplicity, standardization, versatility, no ethical and safety concern and patient-specific therapies. Chemical transdifferentiation has been successfully applied to various cell types across different tissues and organs, and its potential applications are rapidly expanding as scientists continue to explore new combinations of small molecules and refine the mechanisms driving cell fate conversion. These applications have opened up new possibilities for regenerative medicine, disease modeling, drug discovery and tissue engineering. However, there are still challenges and limitations that need to be overcome before chemical transdifferentiation can be translated into clinical practice. These include low efficiency and reproducibility, incomplete understanding of the molecular mechanisms, long-term stability and functionality of the transdifferentiated cells, cell-type specificity and scalability. In this review, we compared the commonly used methods for cell transdifferentiation in recent years and discussed the current progress and future perspective of the chemical transdifferentiation of somatic cells and its potential impact on biomedicine. We believe that with ongoing research and technological advancements, the future holds tremendous promise for harnessing the power of small molecules to shape the cellular landscape and revolutionize the field of biomedicine.
Keywords: cell reprogramming; epithelial–mesenchymal transition; small molecule; transdifferentiation.