Changes

Varying the transfected genes has also shown promise in improving iPSC generation.  For example, culturing the cells with valproic acid allows c-Myc to be excluded from the transfection vector, greatly reducing tumorigenecity at the expense of efficiency.  Alternatively, substituting LIN28 for c-Myc and Klf4 has been shown to increase transduction efficiency and reduce tumorigenicity (c-Myc and Klf4 being [[oncogenes]])<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159104/pdf/ars.2010.3814.pdf</ref><ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924949/pdf/nihms-219126.pdf</ref>.

Varying the transfected genes has also shown promise in improving iPSC generation.  For example, culturing the cells with valproic acid allows c-Myc to be excluded from the transfection vector, greatly reducing tumorigenecity at the expense of efficiency.  Alternatively, substituting LIN28 for c-Myc and Klf4 has been shown to increase transduction efficiency and reduce tumorigenicity (c-Myc and Klf4 being [[oncogenes]])<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159104/pdf/ars.2010.3814.pdf</ref><ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924949/pdf/nihms-219126.pdf</ref>.

Some recent methods have dispensed with transfection altogether, using recombinant protein growth factors instead<ref>http://masspec.scripps.edu/publications/news_art/2009_04_CellSteml.pdf</ref>.  These methods are safer for therapeutic use, as the resulting cells are much less tumorigenic than transfected iPSCs; however they are usually far less efficient than methods relying on transfection.

Some recent methods have dispensed with transfection altogether, using recombinant protein growth factors instead<ref>http://masspec.scripps.edu/publications/news_art/2009_04_CellSteml.pdf</ref>.  iPSCs generated with protein growth factors are sometimes referred to as ''protein induced pluripotent stem cells'' (piPSCs) to differentiate them from iPSCs generated by transfection.  These methods are safer for therapeutic use, as the resulting cells are much less tumorigenic than transfected iPSCs; however they are usually far less efficient than methods relying on transfection.

Regardless of the method used, the mechanism of de-differentiation is the same.  The cultured cells are induced to epigenetically reprogram themselves from a non-dividing (or slowly dividing) terminally differentiated state into an actively [[cell cycle|cycling]] pluripotent state<ref>http://www.bu.edu/abl/files/annual_review_gen.pdf</ref>.

Regardless of the method used, the mechanism of de-differentiation is the same.  The cultured cells are induced to epigenetically reprogram themselves from a non-dividing (or slowly dividing) terminally differentiated state into an actively [[cell cycle|cycling]] pluripotent state<ref>http://www.bu.edu/abl/files/annual_review_gen.pdf</ref>.