NIH Researchers have discovered bone-generating stem cells in the spine, at the end of the shins and in cartilage-rich areas of other bones. They also identified factors that control the growth of these stem cells, according to a report published (4/26/10) in the Proceedings of the National Academy of Sciences. The potential for this market is HUGE and will continue to grow as the population ages and minimally invasive surgeries and shorter hospital stays become a new standard.
The current study is the 1st to identify the location of bone stem cells in the adult mouse skeleton; the researchers refer to the newly identified cells as bone stromal cells. “Stroma” is a term used to describe a supportive or connective structure in biological tissue. The term distinguishes the cells from hematopoietic stem cells, which give rise to blood cells and which are found in bone marrow.
The researchers undertook the study to learn more about the role of 2 genes, dubbed Prkar1a and prkaca, in a key chemical sequence that provides energy to cells. Prkar1a has been implicated in a variety of rare human cancers, of the bone, nervous system, and thyroid:
- When the 2 genes are working normally, bone cell growth proceeds normally and cancerous overgrowth is kept in check. In previous research, the researchers learned that tumors formed in numerous tissues when they inactivated prkar1a,
- In the current study, they inactivated 1 copy each of the 2 genes. Like human beings, mice have 2 copies of most genes. The mice in the study had 1 functioning copy each of prkar1a and prkaca and 1 non-functioning copy of each gene.
The researchers predicted that disabling only 1 copy of each gene would offer protection from bone tumor growth. In fact, the combination had the opposite effect:
- Tumorous growths were unexpectedly prolific and developed much earlier than expected: Tumors appeared in mice as young as 3 months old, compared with 6 to 9 months old in the previous studies, in which only prkar1a had been inactivated,
- Moreover, abnormal growths formed near cartilage in the legs, along the tail, and the remaining vertebrae of the mice. The bone tumors were also more extensive in the mice with the 2 inactivated genes compared with their counterparts having only a single inactivated gene,
- All mice with the 2 mutations had abnormal growths on their tail bones by the time they were 9 months old and showed abnormalities in their vertebrae by 12 months,
- Examination of the tumor cells and of cells from the same locations in mice that did not have tumors confirmed that the cells were bone stem (stromal) cells. Specifically, proteins on the surface of the cells were identical to proteins found on other types of stem cells. Moreover, the tumors formed only at locations where bone is actively growing, even in the adult mouse skeleton.
”Identifying the location of bone stem cells and some of the genetic triggers that control their growth is an important step forward,” said. “Now, researchers can explore ways to harness these cells so that ultimately they might be used to repair damaged or malformed bone. Also, studies of this stem cell population could yield insight into the formation of bone tumors (Alan E. Guttmacher, M.D., of the NIH) “The findings open up 2 avenues for additional research to identify the chemical signals that initiate the formation of new bone tissue could lead to new techniques for regenerating damaged or injured bone. (First author is KM Tsang, Laboratory of Dr. Stratakis)