A stem cell capable of regenerating both bone and cartilage has been
identified in bone marrow of mice. The discovery by researchers at Columbia
University Medical Center (CUMC) is reported today in the online issue of the
The cells, called osteochondroreticular (OCR) stem cells, were discovered by
tracking a protein expressed by the cells. Using this marker, the researchers
found that OCR cells self-renew and generate key bone and cartilage cells,
including osteoblasts and chondrocytes. Researchers also showed that OCR stem
cells, when transplanted to a fracture site, contribute to bone repair.
"We are now trying to figure out whether we can persuade these cells to
specifically regenerate after injury. If you make a fracture in the mouse,
these cells will come alive again, generate both bone and cartilage in the
mouse—and repair the fracture. The question is, could this happen in humans,"
says Siddhartha Mukherjee, MD, PhD, assistant professor of medicine at CUMC and
a senior author of the study.
The researchers believe that OCR stem cells will be found in human bone
tissue, as mice and humans have similar bone biology. Further study could
provide greater understanding of how to prevent and treat osteoporosis,
osteoarthritis, or bone fractures.
"Our findings raise the possibility that drugs or other therapies can be
developed to stimulate the production of OCR stem cells and improve the body's
ability to repair bone injury—a process that declines significantly in old
age," says Timothy C. Wang, MD, the Dorothy L. and Daniel H. Silberberg
Professor of Medicine at CUMC, who initiated this research. Previously, Dr.
Wang found an analogous stem cell in the intestinal tract and observed that it
was also abundant in the bone.
"These cells are particularly active during development, but they also
increase in number in adulthood after bone injury," says Gerard Karsenty, MD,
PhD, the Paul A. Marks Professor of Genetics and Development, chair of the
Department of Genetics & Development, and a member of the research team.
The study also showed that the adult OCRs are distinct from mesenchymal stem
cells (MSCs), which play a role in bone generation during development and
adulthood. Researchers presumed that MSCs were the origin of all bone, cartilage,
and fat, but recent studies have shown that these cells do not generate young
bone and cartilage. The CUMC study suggests that OCR stem cells actually fill
this function and that both OCR stems cells and MSCs contribute to bone
maintenance and repair in adults.
The researchers also suspect that OCR cells may play a role in soft tissue
The authors declare no financial or other conflicts of interest.
The study was funded by grants from the National Institutes of Health (5U54
CA126513, R01 RHL115145A, AR056246, and EB006834), the Robert Carroll and Jane
Chace Carroll Laboratories, the American Cancer Society, the NH&MRC and
Menzies Foundation, Cancer Council SA's Beat Cancer Project on behalf of its
donors and the State Government of South Australia through the Department of
Health, Gastroenterological Society of Australia, the American
Gastroenterological Association, the American Association for Cancer Research,
the Royal Australasian College of Physicians, and the Columbia University Ines Mandl
Postdoctoral research fellowship.
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