Sticky cells to heal wounds
Initial 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 called thrombin; this is normally produced in a wound to help blood to clot, which it does by converting a substance from the bloodstream, called fibrinogen, into a sticky meshwork that glues the wound together. The ultimate goal is to take a patient’s own stem cells, culture them in a dish and then endow them with this ability. This means they can then be injected into a wound where they will lay down the repair material and, in the process, enable themselves to better survive and stimulate healing. Chris Smith heard about the challenges in cell therapy, and the importance of this breakthrough, from the University of Bristol's Adam Perriman...
Adam - One of the big challenges in cell therapy, so these are therapies where we use for example patients own cells to treat, is that the environments that the cells face, when either injected or transplanted, are quite aggressive and so we were trying to come up with a way to effectively coat the cells to make them more resistant to those harsh environments.
Chris - Is this like anatomical Velcro for cells; you're decorating cells with molecules that make them stickier and make the environment more receptive to them coming in and living and surviving?
Adam - It is a bit like Velcro. We put on the first molecule, which is what we call an enzyme, and what that does is actually it can take molecules that are naturally in the body and can assemble them into what we call a hydrogel, which is a bit like the jelly that you have in your fridge when you're perhaps making jello shots.
Chris - So what molecule is it you're putting on, to do that?
Adam - So we put on molecule called thrombin. This is a molecule which gets switched on when we cut ourselves - we have a wound, and then it actually causes a second molecule fibrinogen to self assemble into this gel.
Chris - How do you get the thrombin onto the cells in the first place?
Adam - Okay, well that's a great question. We take this thrombin, it's what we call a macromolecule, it's a big protein, and we effectively decorate this molecule with detergent molecules, very specialised detergent molecules similar perhaps to a detergent that you would have in a laundry detergent. And what this does is that it allows these thrombin molecules to basically insert into the membrane of the cells, so the bit that surrounds the cells.
Chris - You end up then, with a cell that is a bit like a spiky meatball; it's got these thrombin enzymes sticking out of the surface so they retain their ability to be an enzyme, to make that fibrinogen turn into sticky fibrin, but they're sticking on the surface of the cells to do it?
Adam - That's right. Actually, what happens, you can literally take this solution of this thrombin and you can incubate the cells, so just mix it with the cells, and then it will spontaneously start to stick and assemble on the surface. And what's interesting about this is that then when we start to form this hydrogel, this special type of material, it actually glues or welds these cells together, and that's what's really different about what we are doing in this research.
Chris - Does it just come down to gluing things in place or does that fibrin meshwork, the matrix that you end up making, does that have other properties in the sense that does it encourage things like blood vessels to come in? Because one of the other things that is a challenge for cell transplantation is making sure that the cells have a ready supply of raw materials brought in by things like the bloodstream.
Adam - Yeah, okay. So fibrin as what we would call the biomaterial is quite special. One of the important components is that it allows cells to actually crawl around and move around in 3D. So cells don't like to just necessarily sit where you put them, they might want to move around and start to if you're growing tissue - a piece of skin - you might need the cell to move around and connect with another cell. They're a bit like computers, they really interpret the localised environment and so there are special types of buttons on a cell and materials like fibrin can sort of push those buttons and tell the cell that it's in a happy place, it's in a good environment to survive.
When it comes down to blood vessel formation, again, this obviously involves cells assembling into tubes and those sorts of systems. Obviously, fibrin again would provide a nice environment for the formation of blood vessels.
Chris - And have you actually tried doing this, what we would dub in vivo, if you take a real world example like a wound or a situation where you would want to graft tissue in, in the living entity, have you actually demonstrated that this has improved performance when you do it like this?
Adam - The initial focus of the paper was on developing the synthetic biology and the chemistry of the molecules, but towards the end of the research we did some experiments on a model organism. So we worked with zebrafish, partly because when they're really young they're transparent so you can image them. So in that situation we actually took fish skin cells, we painted them with our special thrombin, and injected those into a zebrafish and showed that the cells were still viable and it wasn't bad for the zebrafish. But really the next phase of the research will be looking at wound models to see whether or not we can increase wound closure in a model organism like this.