| Departments — Benchmarks | Spring 2008 |
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Weapon for Mass Construction The findings could represent a novel therapeutic strategy for bone diseases: targeting stem cells using drugs. If so, this news may one day help put the spring back in the step of postmenopausal women who suffer from osteoporosis or individuals who have lost bone mass because of cancer. The team of investigators led by Siddhartha Mukherjee ’00, an HMS instructor in medicine at Massachusetts General Hospital’s Center for Regenerative Medicine and Technology, set up their study to examine the effects that the drug bortezamib might have on cells known as mesenchymal stem cells (MSCs). Found in bone marrow, MSCs are multipotent; that is, they can develop into any of several types of cells. If triggered during their more impressionable period, they can become bone, fat, muscle, or cartilage cells that can then grow or repair tissue lost to disease or trauma. The team selected bortezamib because clinical evidence from multiple myeloma patients taking the drug showed elevated serum levels of alkaline phosphatase and osteocalcin, substances linked with bone formation. Hoping to isolate how the drug’s actions might contribute to increased bone formation, the researchers tested possible targets for the drug. Surprisingly, they found it caused MSCs to form bone tissue. The in vivo mouse model the scientists used was one developed for menopausal osteoporosis. When they treated these mice with low doses of bortezamib, doses equivalent to between one-fifth and one-third what would normally be considered effective against tumors, they found an increase in bone formation, in the mineralization of spongy tissue matrices that form the ends of long bones such as the femur, and in the production of osteoblasts, the cells that make up bones. Similar results were achieved when the researchers tested the drug in vitro on cultured MSCs derived from human bone marrow and from mouse models. The authors point out the drug’s potential for people experiencing bone loss. In addition, they note the study offers proof of principle that a drug can harness the inherent power of the body’s stem cells to repair and regenerate tissue—a strategy that might become increasingly key to regenerative medicine. Ann Marie Menting is associate editor of the Harvard Medical Alumni Bulletin Photo: Stockbyte/Getty Images |
Massachusetts General Hospital and the Harvard Stem Cell Institute. A team of researchers wrote in the February issue of the Journal of Clinical Investigation that a drug used as a targeted chemotherapy in patients with multiple myeloma helped regenerate bone tissue in mice by activating stem cells critical to the formation of new bone tissue.
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