Various advantages became apparent in recent reprogramming methods compared to genome integrating viruses like retrovirus and lentivirus. The application of non- or low genome integrating and virus free methods harbors a positive safety aspect in the utilization of iPSCs in clinical implications. The translation of iPSC technology into cell therapeutic applications is becoming more and more important [20]. A still existing huge disadvantage of most of these methods is the low efficiency. One promising integration free method is the use of Sendai RNA viruses, although that this system comes along with possible reactivation of viral genes and shows a rather low reprogramming efficiency [9]. Other methods with low genomic integration are plasmid or episomal transfection, but the risk of a host genome integration cannot be completely eliminated. Moreover, also these systems exhibit a low reprogramming efficiency compared to other systems [10, 21]. Another very different integration free method is the direct delivery of reprogramming proteins into the cells [22]. Nevertheless, this approach is technically difficult and requires high amounts of special proteins. Again protein transfection also shows a low efficiency.
