The build-up of scar tissue makes recovery from torn rotator cuffs, jumper’s knee, and other tendon injuries a painful and challenging process, often leading to secondary tendon ruptures.
New research led by Chen-Ming Fan, of the Carnegie Institution for Science in the USA, and published in Nature Cell Biology, reveals the existence of tendon stem cells that could potentially be harnessed to improve tendon healing and even to avoid surgery.
Working with Carnegie’s Tyler Harvey and Sara Flamenco, Fan revealed all of the cell types present in the Patellar tendon, found below the kneecap, including previously undefined tendon stem cells.
“Because tendon injuries rarely heal completely, it was thought that tendon stem cells might not exist,” said lead author Harvey. “Many searched for them to no avail, but our work defined them for the first time.”
Stem cells are “blank” cells associated with nearly every type of tissue, which have not fully differentiated into a specific functionality. They can also self-renew, creating a pool from which newly differentiated cell types can form to support a specific tissue’s function. For example, muscle stem cells can differentiate into muscle cells. But until now, stem cells for the tendon were unknown.
Surprisingly, the team’s research showed that both fibrous scar tissue cells and tendon stem cells originate in the same space – the protective cells that surround a tendon. What’s more, these tendon stem cells are part of a competitive system with precursors of fibrous scars, which explains why tendon healing is such a challenge.
The team demonstrated that both tendon stem cells and scar tissue precursor cells are stimulated into action by a protein called platelet-derived growth factor-A. When tendon stem cells are altered so that they don’t respond to this growth factor, then only scar tissue and no new tendon cells form after an injury.
“Tendon stem cells exist, but they must outcompete the scar tissue precursors in order to prevent the formation of difficult, fibrous scars,” Fan explained. “Finding a therapeutic way to block the scar-forming cells and enhance the tendon stem cells could be a game-changer when it comes to treating tendon injuries.”
Source: Carnegie Institution for Science
Reference: Tyler Harvey, Sara Flamenco, Chen-Ming Fan. A Tppp3 Pdgfra tendon stem cell population contributes to regeneration and reveals a shared role for PDGF signalling in regeneration and fibrosis. Nature Cell Biology, 2019; DOI: 10.1038/s41556-019-0417-z