The firs method to make human iPSC used a retroviral vector delivery system, carrying the risk of transgene reactivation and insertional mutagenesis. Since then many other groups have used the same methods to reprogram cells to pluripotency among others. After that research efforts focused on searching different ways to induce pluripotency without suffering genetic changes in order to prevent transgenes from reactivating and avoiding the risk of genomic recombination or insertional mutagenesis. Some of these methods are; non-integration adenoviruses, expression plasmids, episomal vectors, piggy Bac transposition, Sendai virus, direct delivery of reprogramming proteins, synthetic modified mRNAs, chemical compounds and synthetic self-replicative RNA replicons
All though a wide range of methods have successfully reprogrammed somatic cells to a pluripotent state only three methods appear to be appropriate for reprogramming patient cells for cellular therapy: Sendai virus, mRNA and episomal vectors.
(Jordi Requena, Ana Belen Alvarez Palomo, Marti Farrera Sal, John Christodoulou, Josep M Canals and Michael J Edel- The Future Challenges for the Clinical Application of Reprogrammed Cells)
Last date updated on June, 2014