For years, medical researchers have been searching for a way to study the effectiveness of stem cell therapies without testing them on humans. But it's difficult, and many problems pop up, including the fact that many animals reject the stem cell grafts or transplants.
MU researchers Dr. R. Michael Roberts and Dr. Randall S. Prather believe they've found the answer: The two have collaborated to create a genetically modified pig with an immune system that doesn't allow rejection.
I sat down with the two researchers to discuss how these genetically modified pigs and this study will help further the research on stem cell therapy.
What is the main problem with stem cell research that your study is trying to overcome?
Prather: One of the problems that people encounter is that the stem cells, when they're transferred to the recipient, they get rejected. And so we tried to create a pig that would not have that rejection process. In addition, one of the problems that can be encountered with stem cells is putting it in a model system that would replicate what occurs in humans.
Prather: And before these pigs were created, the main system that people used was mice and there are a lot of problems with that in terms of size and just the rejection process.
Roberts: There are technical difficulties in where to place the cells in the animal so that they form a graft, and also, the fact as Dr. Prather said, the mouse, which has been the commonest animal used, really is inappropriate for a lot of things that physicians eventually would want to do with these cells. Physicians would also like to practice on a larger animal than a mouse for doing surgical preparations and so on.
So how are pigs more similar to humans other than size?
Roberts: The pig is similar in everything from its digestive system to its immune system to its general lungs, everything ,is of greater resemblance to the human than the mouse, and therefore it's a much much better model.
Prather: The size is a big issue, because we have some collaborators who work on eye disease, and they want to be able to transfer stem cells, for example, into the eye to affect a therapy for people that might have retinitis pigmentosa for example. Well, if we have a mouse that we transfer into the eye, the mouse is so small, the eye is so small, how many cells do you transfer, how do you actually do it? Whereas if you have a pig that's similar in size, now you can really transfer in the right number of cells, determine the right number of cells to transfer in, and the techniques and the tools that you develop to do that can readily be applied to humans.
So how did you guys create an immune system in these pigs that keeps the stem cells from being rejected?
Prather: The easy answer is we genetically engineered them so that they cannot make any new antibodies, so they have an innate immune system that's still functioning but to create an antibody to some new pathogen or some new antigen or some new disease they just can't create any new antibodies.
Roberts: Rather than create a new immune system, we actually depleted the immune system of certain pathways. And, as he said, this is the part of the immune system that produces antibodies and also the kind of t-cells, which are a type of lymphocyte that would attack the graft.
So what does this mean for stem cell research now? Now that you've done a study where stem cells aren't rejected by pigs, how much more needs to be done before it can be applied to humans?
Prather: Well I think you're asking a couple different questions. One question is, how can the pig be used, and the other question is, how can the stem cell be used? And the pig's available, and people can use it, and we've had requests literally from around the world to be able to have access to these animals to develop whatever stem cell therapy that people are trying to put into play so that they can treat certain human ailments.
Prather: So I said we created the animals, but what you have to understand is once these founder animals are created, you don't have to go through that process anymore. You can just use proper breeding to propagate that genetic mutation into additional animals that can be used for research.