Tomoki  Takashina,Yukihito  Ishizaka,
Advances in direct reprogramming and its future clinical application using a protein-based cell engineering system
International Journal of Regenerative Medicine
2018
2613-5914
http://dx.doi.org/10.31487/j.RGM.2018.02.005
https://www.sciencerepository.org/advances-in-direct-reprogramming-and-its-future-clinical-application-using-a-protein-based-cell-engineering-system_RGM-2-105 
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.Keywords: Direct reprogramming, NTP, artificial transcription factor, expansion