A newly discovered small molecule called IQ-1 reportedly plays a key role in preventing mouse embryonic stem cells from differentiating into one or more specific cell types, allowing them to instead continue growing and dividing indefinitely.
This discovery takes scientists a step closer to being able to grow human embryonic stem cells without the “feeder layer” of mouse fibroblast cells, which is essential for maintaining the pluripotency of embryonic stem cells, says the study’s primary investigator, Michael Kahn, Ph.D., Provost’s professor of medicine and pharmacy at the University of Southern California.
“Stem cells that grow on feeders are contaminated with mouse glycoproteins markers,” Dr. Kahn points out. “If you use them in humans, you’d potentially have a horrible immune response.” Thus, to take any eventual stem cell-based treatments from the laboratory to the clinic, there needs to be a way to keep the cells growing and dividing without the use of mouse fibroblasts.
What IQ-1 does, Dr. Kahn explains, is to block one arm of a cell-signaling pathway called the Wnt pathway, while enhancing the signal coming from the other arm of the Wnt pathway. This pathway is known to have dichotomous effects on stem cells; i.e., both proliferative and differentiative. More specifically, IQ-1 blocks the coactivator p300 from interacting with the protein ß-catenin. This prevents the stem cells from being told to differentiate into a more specific cell type. At the same time, IQ-1 enhances the interaction between the coactivator CBP and ß-catenin, which signals the cells to keep dividing and to remain as fully potent stem cells.
“This way, you can essentially maintain the stem cell’s growth and potency for as long as you want,” Dr. Kahn says.
The research was performed at the University of Washington in Seattle by Dr. Kahn and his colleagues along with collaborators from the Asahi Kasei using mouse embryonic stem cells. Their findings are being published in an online edition of the Proceedings of the National Academy of Sciences.
Dr. Kahn notes that subsequent pilot studies using human embryonic stem cells, in collaboration with Dr. Qilong Ying at the Center for Stem Cell and Regenerative Medicine at the Keck School of Medicine, have confirmed that IQ-1 plays a similar role in that system as well.