article = {RGM-2018-2-105} title = {Advances in direct reprogramming and its future clinical application using a protein-based cell engineering system} journal = {International Journal of Regenerative Medicine} year = {2018} issn = {2613-5914} doi = {http://dx.doi.org/10.31487/j.RGM.2018.02.005} url = {https://www.sciencerepository.org/advances-in-direct-reprogramming-and-its-future-clinical-application-using-a-protein-based-cell-engineering-system_RGM-2-105 author = {Tomoki Takashina,Yukihito Ishizaka,} keywords = {Direct reprogramming, NTP, artificial transcription factor, expansion} abstract ={Direct reprogramming is a promising technology in regenerative medicine. However, there is no report on the clinical applications of cells prepared by direct reprogramming. In the current review, we describe direct reprogramming methods of somatic cells to hepatocytes, pancreatic -cells, cardiomyocytes, and endothelial cells. Next, we discuss current issues that should be clarified for their future clinical applications. As the most critical issue, it is necessary to establish a vector-free system for cellular engineering, because most studies on direct reprogramming have been performed using viral vectors or plasmid DNA. We recently developed a protein-based cell engineering system, in which a newly identified cell penetrating peptide (NTP) was combined with an artificial transcription factor system (NTP-ATF). By using NTP-ATF, endogenous gene expression can be induced by exogenous recombinant proteins. Here, we briefly introduce the NTP-ATF system and discuss its future applications by combining chemical compounds that are competent for the induction of differentiation. We also propose that the NTP-ATF system can be utilized for expansion of somatic cells, which is another issue for cell therapy using somatic cells.}