External Cues Can Replace Genetic Manipulation for Cell Reprogramming

Cell biologists seeking to transform differentiated adult cells back to cells that resemble embryonic stem cells, have begun the process of replacing virally transmitted genes with environmentally supplied growth factors.

The current state-of-the art is to generate induced pluripotent (IPS) cells by reprogramming adult cells through the use of viruses to transfer four genes (Oct4, Sox2, c-Myc, and Klf4) into the cells' DNA. This process is both inefficient and potentially dangerous in that the retroviruses used for gene transfer are potentially carcinogenic, and c-Myc is a known oncogene whose overexpression can also cause cancer.
In the current study, investigators at the Massachusetts Institute of Technology (MIT; Cambridge, MA, USA) left c-Myc out of the formula, replacing it with the protein-signaling molecule Wnt3a. Wnt3a was supplied as an additive to the cells' culture medium rather than as a product of gene transfer.

Results published in the August 6, 2008, online edition of the journal Cell Stem Cell revealed that Wnt3a was able to replace the c-Myc oncogene and, in conjunction with the other three transfected genes, induce the formation of IPS cells.

"IPS cells hold great potential for future medicine, but we must learn how to generate these cells in a manner that is safe for clinical therapies,” said contributing author Dr. Richard Young, professor of biology at MIT. "This advance in reprogramming is one key step toward that goal.”

The investigators concede that while these results mark a good start toward using external cues instead of genetic manipulation to reprogram cells, it is still necessary to eliminate the need for retroviruses for the three other genes.

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Massachusetts Institute of Technology