Induced pluripotent stem (iPS) cells are generally created by the expression of a small number of key genes to reprogram adult cells into an undifferentiated, pluripotent state. Because some of the transcription factors used for reprogramming are oncogenes, as well as concerns about mutagenesis due to genomic integration, scientists have been searching for improved methods to create iPS cells. This includes new delivery methods for the required transcription factors and skipping the iPS step altogether by direct intercoversion of cell types. Recently, in a paper published in Cell Stem Cell, scientists at the Scripps Research Institute in California have found a way to create iPS cells using mainly a cocktail of drugs.
Building on previous work done with fully differentiated skin cells (keratinocytes), the authors began with chemicals known to improve reprogramming efficiency, eventually screening several compounds and reducing the number of exogenous genes required. Ultimately, they were able to produce a stem-like cell introducing only the stem cell marker Oct4 and a combination of four drugs. This feat was also accomplished in two other cell types. The resulting cells expressed a number of pluripotency markers and were able to differentiate into cells from all three primary tissue layers, a key sign of “stemness”, and could be differentiated into a specific cell fate, in this case cardiac muscle cells.
Reducing the need for genetic manipulation is one goal of iPS research. With three of the four required genes now replaced with chemical compounds, we are now one step away from removal of Oct4 and the induction of stem cells using only small molecules. With that accomplished, these drugs can be further characterized and refined, offering new insights into the underlying biology of stem cell reprogramming and offering an efficient, reliable way to produce iPS cells while minimizing associated risks.