Stem Cells in Tendon Hold Promise for Injury Repair

Damaged tendons heal slowly and rarely recover their previous strength and integrity. Now scientists have discovered that adult tendons contain a rare subset of stem cells that can be isolated, grown in the lab, and then used to generate tendon-like tissues in mice. The findings point the way toward improved techniques for repairing human tendons damaged by repetitive movements, tears or aging.

Tendons — the strong, flexible straps of tissue that connects muscle to bone — are made primarily of tough, interwoven protein fibrils. Embedded among these long chains are tendon cells, which produce a unique mixture of proteins, called the extracellular matrix. Researchers led by scientists at NIH's National Institute of Dental and Craniofacial Research (NIDCR) suspected from previous studies that the extracellular matrix must be the home of tendon stem cells, although no such cells had yet been found.

In a paper published online in Nature Medicine on September 9, 2007, the researchers reported that they successfully isolated small numbers of cells with stem cell characteristics from the extracellular matrix of both mouse and human tendons.

"Cells must meet very specific criteria to be termed stem cells," says NIDCR cell biologist Dr. Yanming Bi. "They must produce copies, or clones, of themselves. They must be self renewing, or proliferate extensively. Finally, they must display certain proteins on their cell surface that indicate a capacity to differentiate into other tissues, such as bone and cartilage."

A series of experiments confirmed that the newly isolated cells met all of these criteria. The researchers then grew larger quantities of the self-renewing cells in the laboratory and transplanted them under the skin of mice. Both the mouse and the human stem cells formed tendon-like tissues in the animals. When the human cells were transplanted on the surface of mouse bones, they formed tendon-like attachments.

The scientists also showed that the extracellular matrix helps to create a unique biochemical habitat, or niche, that directs stem cell growth into healthy tendon. When the researchers disrupted this niche, by creating genetically altered mice that lacked two important matrix proteins, tendon formation in the animals went astray. The stem cells began to form bone within the mouse tendon tissue. The scientists thus confirmed that the composition of the extracellular matrix helps to direct stem cell fate.

"As millions of Americans know first hand, torn tendons are much slower to heal than bone injuries, in part because tendons are so blood-vessel poor, and that inhibits the regenerative process," says NIDCR's Dr. Marian Young, the study's senior author. "Using stem cells to create new tendon gets around that problem. But to reach that point, there's a lot of biology and uncertainty that will need to be worked out."