The first steps towards developing a better way to use transplanted cells to repair wounds and regenerate tissues has been developed by scientists at the University of Bristol...
The breakthrough was coating the cells with a molecule found naturally in the body called thrombin. This is produced at wound sites and its role normally is to help blood to clot, which it does by converting a component from the bloodstream, called fibrinogen, into a sticky meshwork that traps blood cells and glues the wound together.
"The environment that transplanted cells face is quite aggressive, and we were trying to come up with ways to make the cells more resistant to those harsh environments," explains Bristol researcher Adam Perriman, who led the study published this week in Nature Communications.
When cells are endowed with additional thrombin and injected into a wound site, they convert the nearby fribrinogen into a jelly-like hydrogel. "Kind of like the stuff you put in the fridge when you're making jello-shots!"
This acts as a scaffold that can support the cells and enable them to grow and interact in three dimensions. It also helps to weld the wound tissues together and promote the growth of new blood vessels, all of which can aid in wound repair.
To get the thrombin onto the cell surfaces, the Bristol team first mixed thrombin with a mild detergent solution. This creates the chemical equivalent of 'Velcro', making the thrombin molecules sticky so they become embedded in the membranes of any cells that are then added to the mixture.
The result is cells decorated with thrombin molecules projecting from the cell surface. Critically, the thrombin retains its enzymic activity, enabling it to convert fibrinogen encountered locally into fibrin.
The team used this technique to show that they could take adult stem cells, subject them to this new treatment and then differentiate them into specialised cell types, like bone or cartilage cells, demonstrating that the technique works and does not compromise the viability of the cells.
The ultimate goal is to be able to take a patient’s own stem cells and endow them in the culture dish with this fibrin-producing ability. Treated cells can then be injected back into a wound or injury site where they will lay down the repair material and, in the process, enable themselves to better survive and stimulate healing. The approach could be used for applications ranging from fixing worn cartilage in arthritic joints through to promoting wound closure at the site of a surgical procedure.
That this is possible in vivo still remains to be proven. Nevertheless, Perriman has done some initial experiments involving transplanting fibroblast (skin) cells treated using the new technique into zebrafish and showing that they integrate successfully and survive. "It's early days, and we've got a long was to go, but this is an enouraging first step."
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