COULD we stem the tide of ageing by delaying the deterioration of stem cells? A new compound that appears to do just that could help us find ways to protect our organs from age-related wear and tear, experiments in mice suggest.
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.
Bellantuono's team think the molecule works by helping the prions protect the stem cells from the DNA damage associated with normal ageing. When they exposed both treated and untreated cells to hydrogen peroxide - a compound known to cause DNA damage - they found that the treated cells were protected from damage (Stem Cells, DOI: 10.1002/stem.1065).
"You can delay the loss of stem cells' function by manipulating the prion protein," says Bellantuono, who presented the findings at the Aging Online Symposium last month. "In the long term, you may go a long way to maintaining tissue health in [old] age."
It may be some time before the compound can be used to fight ageing, but similar molecules might have a more immediate benefit in stem cell therapies.
"A big problem with using MSCs for therapy is that you need to inject millions of cells, but it's difficult to get millions in a dish," says James Adjaye of the Max Planck Institute for Molecular Genetics in Berlin, Germany. "This molecule lets the cells grow for longer - it's very interesting in that respect."
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