Due to the ethical issues surrounding embryonic stem cells, ways of converting fully differentiated, mature cells into stem cells is a growing area of research. Four transcription genes are currently required to convert mature cells into stem cells, but once these are inserted into a cell, they permanently alter the host cell’s DNA and potentially induce tumors or interrupt functions of other normal genes. One alternative is to use drug-like small molecules to reprogram the cell.

Sheng Ding and co-workers, Scripps Research Institute, USA, have reported a cocktail of small molecules that, with the gene OCT4, enables reprogramming of human skin cells into stem cells. The team found that a combination of PS48, a small molecule activator of 3′-phosphoinositide-dependent kinase-1, and sodium butyrate, a histone deacetylase inhibitor, could enhance the reprogramming efficiency of keratinocytes isolated from human skin or hair follicles over 25-fold.

This allows three out of the four transcription genes to be replaced. Ways to replace OCT4 are now being studied by the team.

• Reprogramming of Human Primary Somatic Cells by OCT4 and Chemical Compounds
  S. Zhu, W. Li, H. Zhou, W. Wei, R. Ambasudhan, T. Lin, J. Kim, K. Zhang, S. Ding,
  Cell Stem Cell 2010, 7(6), 651-655.
  DOI: 10.1016/j.stem.2010.11.015