Pluripotent stem cells have successfully been generated from mouse and human somatic cells by stably or transiently introducing genetic material (see blog “Human iPS cells…”) and subsequently from mouse cells by delivering reprogramming proteins (see blog, “Induced pluripotent stem cells…”). Kim et al have now shown that, in addition to mouse cells, human cell fibroblasts could be reprogrammed to a pluripotent state by the addition of reprogramming proteins. These novel protein-induced human pluripotent stem cells (p-hiPSCs) differentiated into all lineages in culture and the developing embryo.
Creating human iPS cells by delivering reprogramming proteins eliminates genome manipulation and DNA transfection, hopefully making them more suitable for basic research, drug discovery, disease modeling and clinical trials. However, the downfall to this promising method is that p-hiPSC generation was very slow (double the weeks required with viral transduction) and inefficient (only 0.001% compared to 0.01% of input cells seen with virus-based protocols). These pitfalls might be avoided if purified and concentrated reprogramming proteins are used in the future, versus whole-protein extracts used presently. The efficiency of p-hiPSCs generation might also be increased using small molecules, as was done when generating mouse p-iPSC, however chemical treatment may have negative consequences. In addition, this new method needs to be expanded from newborn fibroblasts used currently to include adult tissue. Finally, as with all iPSC lines to date, these p-hiPSCs still need additional comparison to embryonic stem cells and assessment long-term in culture to ensure sample consistency.
Generating iPSCs is a rapidly growing technology, and while there are some technical issues with p-hiPSCs, they hold great promise for both basic research and clinical trials.
1. Kim, et al (2009) Cell Stem Cell