Science1 publisher2 min readPublished
Returning stiffened tendon cells to a soft substrate restores their shape and growth
Queen Mary University of London researchers separated two tendon cell populations and put both on stiff and soft surfaces. Only the cells from the softer interfascicular matrix responded, and much of that change reversed when they were moved back.
The Scientist · Science desk
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What happened
- On stiff substrates the interfascicular cells reorganised their internal structure, quickly shifted expression of genes tied to tendon function and matrix production, and lost proliferative capacity.
- Cells from the collagen fascicles, isolated and tested alongside them, were largely unchanged by the same conditions.
- Moved back onto softer, matrix-like substrates, the interfascicular cells regained their shape and their ability to divide, and some of the gene expression changes were restored.
- The authors state that the work does not show interfascicular cells directly cause tendinopathy and does not offer a treatment, presenting instead an experimental framework for asking those questions.
Compiled by The ScientistSomething wrong?How this is made
Why it matters
- constraint The reversal was obtained by lifting cells onto a softer gel, so the result does not mean that a stiffened tendon in a living limb will soften, or that its resident cells will follow it back if it does.
- decision Anyone screening compounds or measuring stiffness responses in tendon cells now has to declare which population is in the dish, since pooling the two would average away a response only one of them shows.
- capability Other labs get a defined culture system for keeping interfascicular cells in character outside the tissue; without one, a follow-up experiment is measuring cells that have already drifted.
- precedent Equine tendon research gains a specific cell population to test, given the mechanical forces horse tendons take during movement and athletic activity.
Tendon contains regions with distinct physical environments [4]. Fascicles are the bundles of collagen; the interfascicular matrix is the softer tissue between them, connecting one bundle to the next [3]. Cells taken from a whole tendon average those two environments into one dish. The Queen Mary University of London group isolated and maintained the two populations separately, then compared how each responded to changes in mechanical stiffness [2][1].
Keeping them separate is harder than it sounds. Cells change their behaviour once they are out of their native tissue, and the team reports a defined culture framework built to hold the interfascicular cells' characteristics in vitro [11]. That framework is also what makes the comparison usable: both populations come from the same tissue and go onto the same substrates, so a stiffness response that shows up in one and not the other is not a general artefact of culturing cells on something hard [6].
"Our findings show that different tendon cells can respond very differently to changes in their mechanical environment," said Simon Grossemy, the lead researcher [8][16].
Then the cells were moved back. Three changes were reported on the stiff substrate, and after the return to a soft one, two were reported recovered and the third only in part [18]. The two that recovered, morphology and the capacity to divide, are the readouts you can see and count; the partial one is gene expression, including genes for matrix production [5][7]. Whether a cell that looks and divides like an interfascicular cell while still transcribing differently behaves like one in tissue is not settled by this design [7].
Hazel Screen, the principal investigator, said: "The recovery we observed when IFM cells were returned to a softer environment was particularly interesting. It highlights how the physical environment is an important factor in maintaining the behavior and characteristics of these cells." [9][16]
The reversal was produced by lifting cells onto a softer surface, which is a different operation from softening a tendon [7]. The phys.org account does not report the stiffness values used. It also leaves out the size of the proliferation decline, which genes recovered and the species the cells came from [17].
Tendinopathy causes persistent pain and impaired movement in people and in many animals, and it is hard to treat partly because the biological processes behind tendon degeneration are still not fully understood [12][13]. The paper is by S. E. Grossemy and colleagues, in Advanced Science [15].
What to watch
- Whether the gene expression changes that persisted after the move back include the matrix production set.
- A test in intact tendon explants or a live animal, where the tissue is stiffened and the cells cannot be relocated to a new surface.
- Whether other groups can hold interfascicular cells in character with the defined culture framework long enough to run compound tests.