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Turning on adult stem cells may help
repair bone
Potential new approach to
treating osteoporosis, other degenerative conditions
BOSTON - January 25, 2008 - 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, 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.
Media Contacts: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials
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