The use of a drug to activate stem cells that differentiate into bone appears to cause regeneration of bone tissue and be may be a potential treatment strategy for osteoporosis, according to a report in the February 2008 Journal of Clinical Investigation. The study - led by researchers from Massachusetts General Hospital (MGH) and the Harvard Stem Cell Institute (HSCI) - found that treatment with a medication used to treat bone marrow cancer improved bone density in a mouse model of osteoporosis, apparently through its effect on the mesenchymal stem cells (MSCs) that differentiate into several types of tissues.
"Stem cell therapies are often thought of as putting new cells into the body, but this study suggests that medications can turn on existing stem cells that reside in the body's tissues, acting as regenerative medicines to enhance the body's own repair mechanisms," says David Scadden, MD, director of the MGH Center for Regenerative Medicine and HSCI co-director. "Drugs that direct immature cells to become a particular cell type, like in this study, could potentially be very useful."
The study was designed to examine whether the drug bortezamib (Bzb), which can alleviate bone destruction associated with the cancer multiple myeloma, could also regenerate bone damaged by non-cancerous conditions. In their first experiments, the researchers showed that treating mice with Bzb increased several factors associated with bone formation. Similar results were seen when cultured MSCs were treated with Bzb, but not when the drug was applied to cells that were committed to become particular cell types. Found in the bone marrow, MSCs have the potential to develop into the bone-building osteoblasts and several other types of cells - including cartilage, fat, skin and muscle.
Subsequent experiments supported the hypothesis that Bzb increases osteoblast activity and bone formation by acting on MSCs but not on more differentiated osteoblast precursors. Use of Bzb to treat a mouse model of menopausal osteoporosis produced significant improvements in bone formation and density. Since current treatments for osteoporosis - which target differentiated cells like osteoblasts and the osteoclasts that break down bone - have limitations, the ability to direct differentiation of MSCs could be a promising approach to treating osteoporosis and cancer-associated bone loss, the researchers note.
"If the paradigm displayed in this study holds true for other tissues, we may have options for repairing and regenerating sites affected by injury or disease with medications - that would be pretty exciting." says Scadden, who is the Gerald and Darlene Jordan Professor of Medicine at Harvard Medical School.
Siddhartha Mukherjee, MD, of the MGH Center for Regenerative Medicine (CRM) and HSCI is lead author of the study, which was supported by grants from the National Institutes of Health. Additional co-authors are Jesse Schoonmaker, David Seo, Joshua Aronson, and Louise Purton, PhD, MGH-CRM; Noopur Raje, MD, MB, MGH Cancer Center; Julie Liu, Jane Lian, PhD, and Gary Stein, PhD, University of Massachusetts Medical School; Teru Hideshima, MD, PhD, Sonia Vallet, MD, Samantha Pozzi, Shweta Chhetry, Mariateresa Fulciniti and Kenneth Anderson, MD, Dana-Farber Cancer Institute; Marc Wein, Dallas Jone, PhD, and Laurie Glimcher, MD, Harvard School of Public Health; and Mary Bouxsein, PhD, Beth Israel Deaconess Medical Center.
Massachusetts General Hospital (www.massgeneral.org), established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.