Pluripotent stem cells were initially generated from somatic cells by stable viral expression of various transcription factors (1-3). In the months since, a variety of other means to introduce the transcription factors have successfully generated mouse and human iPS cells. These include the use of non-integrating adenoviruses, repeated plasmid transfection and transgene removal following reprogramming (4-8). Avoiding stable viral integration moves the field forwards, however these newer approaches are still limited by low frequencies of reprogramming, residual vector sequences and the additional step of removing genetic vectors after integration. Most recently, Yu et al showed that non-integrating episomal vectors can generate human iPS cells free of vector and transgene sequences (9). Reprogramming without genetic modification may create iPS cells that have more similarity to their human embryonic stem cell counterparts, greater predictability and less risk of cancerous growth. Such attributes of these newly derived iPS cells will hopefully increase their relevance to basic research, drug screening, disease modeling and clinical trials. 

The derivation of vector and transgene-free human iPS cells is an important advance for the field, but the future may still require increased reprogramming efficiencies and alternative methods for iPS cell production. For instance, using exogenous chemical factors would eliminate the need to transfect genes into even episomal DNA. Entirely avoiding transcription factor insertion into cells may be the next step, but these cells too will need to be compared with human embryonic stem cells to confirm that there are no major abnormalities that would limit their applicability. 

1. Yu, et al (2007) Science

2. Takahashi, et al (2007) Cell

3. Park, et al (2008) Nature

4. Stadtfeld, et al (2008) Science

5. Okita, et al (2008) Science

6. Kaji, et al (2009) Nature

7. Soldner, et al (2009) Cell

8. Woltjen, et al (2009) Nature

9. Yu, et al (2009) Science