Physiological Changes: Stem Cells

In adults, when a bone breaks, the repair process involves a dramatic shift in the balance of bone formation compared to bone destruction toward a process that strongly favors bone formation. The bone repair process involves the flooding of the break site with mesenchymal stem cells, which span and connect the broken ends of the bone. If the broken ends are stabilized by a physician or by nature, the mesenchymal stem cells differentiate directly into bone-forming cells (osteoblasts) that are oriented into fabrication sheets by the neighboring blood vessels. If the break is not stable, the mesenchymal stem cells differentiate into a spanning plug of cartilage and connective tissue that serves to stabilize the break site, allowing an outer layer of bone to form around the plug bridging the broken ends of the bone; this bone-cartilage composite tissue is called the repair callus. The cartilage on the inside of the callus further develops into what is called hypertrophic cartilage, and these individual end-stage cartilage-producing cells expire.

As the hypertrophic chondrocytes are expiring, they produce and release chemicals that eventually signal blood vessels and new mesenchymal stem cells to enter this site. This combination of new mesenchymal stem cells and blood vessels creates the microenvironment for the formation of bone where cartilage had previously been located. These events have led to the erroneous generalization that cartilage is replaced by bone, when actually cartilage is replaced by blood vessels and a new batch of mesenchymal stem cells, which later form bone. Eventually, the callus is remodeled and sculpted so that scarless bone is located at the site of the original break and is wholly integrated into the pre-existing bone.

The speed at which these repair events occur is directly dependent on the number of mesenchymal stem cells that come to reside in and form the initial callus. It is observed that a person ten years of age and a person ninety years of age repair bone breaks at different rates. One cause for these rate differences is that the number of mesenchymal stem cells in the vicinity of the bone breaks is vastly different. Thus, bone formation, bone growth, bone homeostasis, and bone repair are all dependent on the number and receptive signaling capacity of mesenchymal stem cells.