New Bone Marrow-Based Stem Cell Identified in Mice that Regenerates Bones and Cartilage in Adults

Researchers at Columbia University Medical Center (CUMC) have discovered a bone marrow-based stem cell capable of regenerating both bone and cartilage in mice. The discovery appeared in the online issue of the journal Cell.

These cells have been called osteochondroreticular (OCR) stem cells, and they were identified in experiments that tracked a protein expressed by these cells. By using this specific protein as a marker for OCR stem cells, the Columbia team found that OCR cells self-renew and produce key bone and cartilage cells, including osteoblasts and chondrocytes. Furthermore, when OCR stem cells are transplanted to a fracture site, they dutifully 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.

Since mice and humans have similar bone biology, Mukherjee and his colleagues are quite confident that OCR stem cells exist in human bone marrow. Further studies could uncover new and effective ways to exploit OCR cells to provide greater ways 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. Wang and his team previously 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.

Mukherjee and his coworkers also showed that adult OCR stem cells are distinct from mesenchymal stem cells (MSCs). MSCs play essential roles in bone generation during development and adulthood. Therefore, researchers thought that MSCs gave rise to all bone, cartilage, and fat, but recent studies have shown that MSCs do not generate young bone and cartilage. This study by Mukherjee and his colleagues suggests that OCR stem cells actually make young bone and cartilage, but both OCR stems cells and MSCs contribute to bone maintenance and repair in adults.

Mukherjee also suspects that OCR cells may play a role in soft tissue cancers.

A research team from Stanford University School of Medicine just released a similar study that used a different methodology to identify the same stem cell type.