In a collaborative effort, researchers have discovered a way to turn on stem cell genes in human skin cells (fibroblasts) without the risk of using viruses or inserting new genes.
The research team comprised of faculty at Worcester Polytechnic Institute's (WPI) Life Sciences and Bioengineering Center (LSBC) and investigators at CellThera, a private company also located at the LSBC.
Their discovery opens a new door for reprogramming cells that could eventually lead to treatments for a range of human diseases and traumatic injuries by coaxing a patient's own cells to repair and regenerate the damaged tissues.
"We show that by manipulating culture conditions alone, we can achieve changes in fibroblasts that would be beneficial in development of patient-specific cell therapy approaches," wrote the authors.
In the study, the researchers turned on the existing, yet dormant, stem cell genes OCT4, SOX2 and NANOG already in the skin cells by lowering the amount of atmospheric oxygen the cells were exposed to, and by adding a protein called fibroblast growth factor 2 (FGF2) to the culture medium.
After the stem cell genes were activated and began expressing proteins, the researchers found that those proteins migrated back into the nucleus of the skin cells, precisely as would occur in induced pluripotent stem cells.
"This was an exciting observation. Having these proteins localize to the nucleus is the first step of reprogramming these cells," said Dr. Raymond Page, research assistant professor of biology and biotechnology at WPI and lead author on the paper.
Surprisingly, the team found that the stem cell genes OCT4, SOX2 and NANOG were not completely dormant in untreated skins cells, as was presumed.
In fact, those genes were sending out messages, but those messages were not being translated into the proteins that do the work of making cells pluripotent.
"This was quite unexpected. Not only does this data force us to rethink what the true markers of pluripotency may be, it suggests there is a natural mechanism at work in these cells regulating the stem cell gene expression. That opens a whole new line of inquiry," said Dr. Tanja Dominko, associate professor of biology and biotechnology at WPI and president of CellThera.
The findings of the study were published online as a "fast track" paper from the journal Cloning and Stem Cells.