A drug for cancer that also encourages stem cells to differentiate into bone-forming cells could potentially be used for treating bone-degenerating disorders like osteoarthritis. An HMS research team led by David Scadden, the Gerald and Darlene Jordan professor of medicine at Massachusetts General Hospital and director of the hospital’s Center for Regenerative Medicine, published these results in the February Journal of Clinical Investigation.
A hematologist–oncologist, Scadden and his team were interested in seeing whether mesenchymal stem cells (MSCs) could be influenced to differentiate into a specific cell type. MSCs are found in the bone marrow and possess the capacity of developing into several tissue types, including cartilage, fat, and bone. Until recently, it has been unknown whether MSCs could be manipulated—pharmacologically or otherwise—to bias their differentiation toward a particular cell type.
Bortezomib (Velcade) is a drug currently used in treating multiple myeloma, an incurable cancer that targets plasma cells within bone marrow. A clinical study conducted last year indicated that the drug had the interesting side effect of boosting bone density in patients.
On the basis of this and a handful of in vitro studies, Siddhartha Mukherjee, first author on the current study and HMS instructor in medicine at the MGH Center for Regenerative Medicine, began to investigate whether bortezomib might also be useful for boosting bone density in bone-degenerating conditions.
He conducted experiments in mice—first implanting MSCs to see if bortezomib could bias their differentiation pattern, then investigating whether the drug could modify bone tissue turnover in a mouse model of osteoarthritis. He found that treatment with low doses of bortezomib had both the ability to bias the differentiation pattern of implanted MSCs toward bone-forming cells in vivo as well as to increase bone formation and reduce bone loss in the mouse model of osteoarthritis.
The researchers report that these results raise the possibility of a new approach for treating bone-degenerating conditions in humans. “The idea of finding a drug that can turn on a particular stem cell population to differentiate is conceptually very exciting,” said Scadden. “If it is possible, stem cell research could have an enormous impact on medical care.”
