Barry Fuller, UCL
Kat - One good reason to understand the physical processes involved in freezing is to use them in organ transplants and tissue archiving, a way that freezing tissues and organs could actually keep them healthier for longer so they can be transplanted to people that need them. But at the moment, only very, very simple things like sperm and egg cells can cope with the freezing process. Now we’re joined by Barry Fuller. He’s Professor in Surgical Sciences at UCL and he’s working on this low temperature preservation of cells, tissues, and organs.
So, tell us a little bit at the moment about how we freeze live tissues and what sort of things we can freeze.
Barry - Well the ability to store cells and tissues at low temperatures, as you say, is really very helpful in many areas of medicine and biology, particularly where we need to transfer cells and tissues between different patients and different institutions. It makes things possible where, in the past, it wasn’t possible. So for the future, we hope there are many ways that we can build on this little bit of knowledge that we have already and take this forward into new areas of regenerative medicine and stem cell biology for the future.
Kat - Now I actually used to work on very early embryos and I know that you can freeze a little ball of cells, an embryo, for several years even and then thaw it, transplant it into a lady and it will grow into a baby. Why can't we freeze tissues like say a liver or a heart, and bring them back?
Barry - Well you're right. We can freeze embryos but we had a lot of learning to do to be able to do that. We needed to understand a little bit about the anti-freezes, or cryo-protectants, the need to have them inside the cell and around the cell. And also, control the rate of cooling, the way that heat moves in the system, and the way that ice forms. This is because the fundamental problem is the way that water transmits into ice at very low temperatures. So we had to learn how to do that by controlling physical events to make it successful even for small cells. Moving up the scale to large tissues and organs, we haven’t yet been able to make the engineering work to have that exquisite control of cooling and warming that we need.
Kat - Is that because it’s difficult just to get all the cells in a larger piece of tissue with all the cryoprotectants in them, and cool them all down at the same speed?
Barry - Exactly right, because we’ve learned to avoid the formation of ice as much as possible. Getting the right anti-freezes and getting the control of cooling, we can get living cells and tissues to very low temperatures with small amounts of ice and then they go to a glassy state. The residual water goes glassy, so we avoid the problems of ice. In small samples of cells and embryos, in something like 100 micro litres you can easily control the cooling and warming exquisitely. If you have something the size of a human liver however, of a kilogram, it becomes really very difficult to have that exquisite control across the whole of the organ.
Kat - So what sort of things are you looking at to try and enable this in larger organs and allow more tissues to be cryo-preserved in the future?
Barry - Well one of the things we’re doing is working with engineers to look at varying the rates of temperature change in larger volumes, so that we can induce this glassy state in a more controlled way. In the past, we’ve tended to simply use a slow linear cooling rate because it was easy to produce. Understanding where the damage areas are in the low temperature scale is helping us focus on different parts of the cooling chain and possibly manipulate those rates of cooling at different parts of the overall cycle, so we’re moving away from a linear to a nonlinear profile.
Kat - So that's not just sticking something in the freezer - you're trying to control even different regions of say, a liver, to cool them?
Barry - Different parts of the cooling cycle, having slower or faster regimen so that the size of the tissue or organ won't lose control of temperature change because as you know, if you put a liver into a normal freezer, the outside will freeze very quickly and the centre will stay unfrozen for many hours. So, we need to be able to make sure that everything transmits across the whole of the organ in terms of cooling.
Kat - And just to sort of explain why this is so important, I understand that at the moment say, if you have an organ for transplant, you can only keep it alive outside the body for a couple of days at the most. Why would it be so useful to be able to freeze organs or keep them preserved at lower temperatures for longer?
Barry - Well we can't freeze organs as we just said. We can store them in special liquids just above freezing – about 4 degrees centigrade – making sure that these special solutions are around all the cells in the organ. That helps to prevent some of the injury of the cooling and the fact that the organ is outside the body, it’s not receiving oxygen. What we’re trying to do now is to reproduce a life support system for the organ at low temperatures which will pump around oxygen and nutrients, and try and keep the organ in a better state at low temperatures. Because our cells and bodies, our organs, can use oxygen and molecules like glucose at low temperatures, very slowly, but they can use them. So we need to be able to resuscitate those organs to keep them in the best possible quality for the patient that's going to receive them.