Stem Cells in Tendons (Plus some education)

The National Institutes of Health (NIH) reported last week that scientists have isolated stem cells from tendons which help in the growth and repair of those structures. The abstract of the peer-reviewed report, "Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche," is curently available at Nature Medicine at Advance Online Publication. (Later readers of this post will need to search at Nature Medicine for updated location.)

Once again, we have confirmation that tissues that grow, remodel and repair themselves after birth have stem cells that are available for research and which may soon be harvested from injured patients and utilized in medical treatments.

From "Monsters and Critics,"

Songtao Shi identified unique cells within the adult tendon that have stem-cell characteristics -- including the ability to proliferate and self-renew.

The researchers were able to isolate the cells and regenerate tendon-like tissue in an animal model.

'Clinically, tendon injury is a difficult one to treat, not only for athletes, but for patients who suffer from tendinopathy such as tendon rupture or ectopic ossification,' Shi said. 'This research demonstrates that we can use stem cells to repair tendons. We now know how to collect them from tissue and how to control their formation into tendon cells.'

The NIH press release is the most interesting to me (probably because I haven't had a sprained ankle in a while), because of the discussion of "niches" and the conclusion of one of the authors to "follow the phenotype." (More on this phrase, later.)

From the NIH press release:

Marian Young, Ph.D., an NIDCR scientist and the senior author on the study, said the findings also bring to light an unexpected biochemical habitat, or niche, that harbors stem cells. The cells are embedded between layers of extracellular matrix (ECM), the chain-like coils of protein that give tendon its elasticity and contain relatively few cells or blood vessels. To date, most known adult stem cells occupy cell-rich environments with a ready source of nutrients.

"We read a lot about the promise of stem cells, but sometimes overlooked is the importance of the niches that surround them," said Young. "Each individual niche in the body helps to carefully regulate the activities of a given stem cell. What�s nice is we have begun to characterize both in tandem, and that gives the field a head start in learning to meld an understanding of both and hopefully one day to re-engineer damaged tendon."

According to Young, the stem cells, which her group named tendon stem/progenitor cells, or TSPCs, would have never been discovered had it not been for their studies with mice — and good fortune. Young�s laboratory for several years had been knocking out, or inactivating, specific genes in developing mice that likely were involved in forming skeleton and its associated tissues. Among these genes were those that encoded the structural proteins biglycan and fibromodulin, major components of the ECM.

Having knocked out the genes for biglycan and fibromodulin in a new litter of mouse pups, they noticed the mice developed an unusual gait and had difficulty flexing their limbs at two months old. Subsequent X-rays provided the reason: Without biglycan and fibromodulin, the mice were abnormally forming bones within their tendons.

Young and her colleagues theorized that the tendons in these mice might contain stem cells that normally form tendon and, when their niche is altered, misguidedly create bone. If so, they theorized the ECM might house the stem cells, and biglycan and fibromodulin likely played a key role in regulating their normal activity.

The article goes on to quote Dr. Young as saying, "The lesson here is: Follow the phenotype."

If I understand correctly, Dr. Young is confirming that in order to produce stem cells and progenitor cells that will be useful and therapeutic in human patients, we will need to understand and/or be able to reproduce or influence the actual environment where the stem cells develop. Rather than focusing so much of our research efforts and money on embryos, we should be looking at the normal and abnormal local conditions that we want to treat: the "extracellular matix," the local chemical, hormonal, and physical conditions which surround the body's own stem cells and which may be tweaked to induce healing in place, in the patient.