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Scientists Use Proteins to Stimulate Skeletal Stem Cells

Accepted submission by takyon at 2015-11-23 23:22:16
Science

University of Southampton scientists are developing a new type of drug that may help bones heal faster by activating a stem cell regeneration gene [southampton.ac.uk]:

Using bone samples from people undergoing hip replacement surgery, the researchers were able to show that the drug – a protein that activates a molecular pathway called the 'Wnt' pathway – causes stem cells found within bones to divide and to turn into more bone cells.

Dr Nick Evans, Associate Professor in Bioengineering at the University of Southampton and lead author of the study, says: "Bone fractures are a big problem in society, especially in older people. It is getting worse as more people get older and their risk of fracture increases. Most fractures heal completely by themselves, but a surprising number, around 10 per cent, take over six months to heal, or never heal at all. In the worst cases this can lead to several surgical operations, or even amputation.

"Through our research, we are trying to find ways to chemically stimulate Wnt signaling using drugs. To achieve this, we selectively deliver proteins and other molecules that change Wnt signalling specifically to stem cells, particularly in the bone. This may help us find cures for many diseases, including bone disease, and speed up bone healing after fracture."

However the researchers found that if the Wnt pathway was switched on too long, the regenerative effect was lost or, even reversed. "This is why it is particularly important to develop technologies for timed and targeted delivery, which is what we have done in this research," Nick added. The research is published in the journal Stem Cells.

More about the Wnt signaling pathway [wikipedia.org] and PubMed search for WNT3A [nih.gov].

Transient Canonical Wnt Stimulation Enriches Human Bone Marrow Mononuclear Cell Isolates for Osteoprogenitors [wiley.com] [abstract]

[...] Wnt stimulation resulted in an increase in the frequency of skeletal stem cells marked by the STRO-1bright/Glycophorin A phenotype. Osteogenesis was elevated in stromal cell populations arising from BMMNCs transiently stimulated by Wnt3A protein, but sustained stimulation inhibited osteogenesis in a concentration-dependent manner. These results demonstrate that Wnt stimulation could be used as a therapeutic approach by transient targeting of stem cell populations during early fracture healing, but that inappropriate stimulation may prevent osteogenesis.


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