Within all the promise and hope of embryonic stem cells lies a dangerous catch-22. Their pluripotency and ability to self-replicate makes them a potential gold mine for cures, but also causes the formation of teratomas. But a new study performed at the University of California, San Diego (UCSD) has been able to reduce the size and number of them formed after implantation, an important first step to eradicating them completely.
Teratomas are benign tumors containing cells from each of the three germ layers, and are considered by the FDA to be one of the biggest obstacles to stem cell–based medicine. Before implantation, stem cells are guided to differentiate into the type of cell required for treatment. But since differentiation is a process that is never truly complete, the implanted cells contain a mixture of cells. When this mixture is implanted, it can lead to the formation of teratomas.
Yang Xu, a biology professor at UCSD, led a team of researchers to try to solve this problem. What they found evidence that the prevention of these tumors is possible.
“To eliminate the residue of undifferentiated embryonic stem cells during the differentiation, it is important to elucidate the pathways that are important to maintain the self-renewal of embryonic stem cells,” Xu told BioTechniques. “This is exactly what we did.”
The team identified a new signaling pathway that the undifferentiated cells use for propagation, which depends upon the phosphorylation of the transcription factor Nanog; this is crucial for cell replication. But by inhibiting this pathway with small-molecule compounds, they were able to see a stark difference in the resulting teratomas.
“There was a 70% reduction in mass,” said Xu, “and more importantly, the elimination of the self-renewing stem cells in the teratomas.”
At this point, said Xu, he considers the team’s work to be a proo-of-concept. However, he hopes that through more testing and the discovery of new pathways, teratomas can be eliminated completely from stem cell–based therapies, making them safer for use in human disease applications.
The paper, “Phosphorylation stabilizes Nanog by promoting its interaction with Pin1,” was published on the PNAS website on July 6.