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Researchers Isolate Adult Stem Cells for First Time in Tendon


Tendon, the cord-like tissue that connects muscle to bone, contains a small subset of previously unknown adult stem cells, scientists at the National Institute of Dental and Craniofacial Research (NIDCR) part of the National Institutes of Health, and their colleagues have discovered.  

The finding, published online today in the journal Nature Medicine, points to a natural  source of tendon-producing cells in adults and raises the possibility that, with further research, these cells one day could help to mend torn or degenerating tendons that are slow to heal.

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.  To test this theory, Young said she sought the help of her colleague Songtao Shi, DDS, Ph.D., now a scientist at the University of Southern California, who had previously discovered stem cells in adult dental tissues.

Their speculations turned out to be correct.  Yanming Bi, Ph.D., a cell biologist in Young’s laboratory, isolated various cells from mouse and human tendon and cultured them in the laboratory.  “Cells must meet very specific criteria to be termed stem cells,” said Bi, the lead author on the Nature Medicine paper.  “They must produce copies, or clones, of themselves.  They must be self renewing, or proliferate at a rapid rate.  Finally, they must display certain proteins on their cell surface that indicate a capacity to differentiate into other tissues, such as bone and cartilage.”

 

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