Cell reprogramming by proteins conjugated nanotubes

Abstract

The potential of induced pluripotent stem cells is enormous, but many obstacles should be overcome remain before their medical and pharmaceutical applications can be fully realized. To address the safety issues arose from harboring integrated exogenous sequences in the target cell genome, a number of modified genetic methods have been developed and produced induced pluripotent stem cells with potentially reduced risks. However, all of the methods yet developed involve the use of genetic materials and thus the potential for unexpected genetic modifications by the exogenous sequences in the target cells. Recently one possible way to avoid introducing exogenous genetic modifications to target cells was reported. They deliver the transcriptional proteins directly into cells by conjugating them with a short peptide that mediates protein (protein transduction domains; PTD) transduction, such as poly-arginine, In contrast to virus- or gene-based methods, the reprogramming factors were not provided continuously and thus were in short supply. Therefore, they chose repeated protein treatment cycles every 2 day or 16 hrs. The efficiency of induced pluripotent stem cells generation is 10 times lower using this protein based protocol (about 0.001% of input cells), compared to virus-based protocols (about 0.01% of input cells). The gene vector-free, direct protein transduction system eliminates limitations that may be caused by viral or any other gene-based reprogramming methods. However, the generation of protein-based induced pluripotent stem cells is very slow and inefficient and requires further optimization. In this study, we suggested a delivery system transfer transcriptional factors into cell more effective than PTD system. Requisites for the delivery system carrier are cell membrane permeability (nanomaterials), having wide space to load material, low cell toxicity. Nanomaterials have drawn particular attention their small and uniform dimension to apply biological f...