New Prion Therapy Reverses Aging-Related Deterioration of Stem Cells in Mice
As we age, so do our mesenchymal stem cells (MSCs): their numbers in our bone marrow decline, and those that are left lose the ability to differentiate into the distinct cell types - such as bone, cartilage, fat and possibly muscle cells - that help in the healing process.
“We think this ageing of stem cells may be linked to the onset of some age-related disorders, such as osteoporosis,” says Ilaria Bellantuono at the University of Sheffield in the UK.
Earlier research in mice had suggested that the prion protein expressed by MSCs might play a role in holding back stem cell ageing. Mice lacking the prion protein were less able to regenerate blood cells.
The study provided more evidence that correctly folded prions serve a useful purpose in the body, despite the role that misfolded prions play in BSE and vCJD.
Bellantuono and her colleagues have now found that the prion protein performs a similar function in humans - older MSCs from human bone marrow expressed less of the protein than younger ones.
In a bid to find a compound that might slow MSC ageing, the team tested numerous molecules known to target prion proteins on dishes of human stem cells. One molecule emerged as a potential candidate - stem cells treated with it produced 300 times the number of cells over 250 days than untreated stem cells. The treated cells kept on dividing for longer.
The team then injected treated cells into the thigh bones of mice, and three days later found that they had produced three times as many new cells as they would normally produce. After five weeks, there were 10 times as many cells.
The new cells appeared to be of higher quality, too, and readily differentiated into bone and fat cells, as well as those that support the tissue and blood vessels.