Inter-species transplant reverses diabetes

A replacement pancreas that cures diabetic mice has been grown successfully in an animal of a different species by scientists in Japan. Tomoyuki Yamaguchi and his colleagues injected mouse stem cells into developing rat embryos. Once the rat had developed they were able to transplant the pancreas tissue into a group of diabetic mice, fixing their blood sugar levels for more than a year. Qiao Zhou, a stem cell biologist at Harvard University but who wasn't involved in the research, took Chris Smith through what the Tokyo-based team have achieved…

Zhou - What it did essentially is we managed to grow a mouse pancreas in a rat. Then we subsequently harvested this mouse pancreas from the rat and transplant it into a diabetic mouse and was able to show that this can reverse the diabetes of the recipient mouse.

Chris - Now why is that a breakthrough?

Zhou - First of all this has never been done before. This whole process, I think, points to a potential way to grow organs for future clinical use in human organ transplantation. I think that’s the exciting part of it. It’s a proof of concept.

Chris - How did they do it?  

Zhou - The way they did is they took a mouse pluripotent stem cells, also called embryonic stem cells that are capable of giving rise to all tissue and body parts, and injected them into a very early stage rat embryo. At this point the embryo is just a ball of cells. The mouse injected stem cells intermingled with the resident rat stem cells and together they gave rise to a rat. But in this rat, which is called a chimeric rat, every tissue and body part has both rat cells and mouse cells. This is true for pancreas normally, you will have a normal mixture of rat cells and mouse cells, except in this case, the scientist used a method to suppress the growth of the rat pancreas so that the pancreas itself is entirely, or almost entirely made up of mouse cells.

Chris - And it was from that mouse pancreas tissue that they then extract this mouse pancreas and put that back into other mice to show that it works as pancreatic tissue capable of controlling their blood sugar?

Zhou - Yes, exactly. They didn’t use the entire pancreas, but groups of cells, so-called endocrine cells. These are the hormone secreting component of the pancreas that secrete insulin to regulate blood glucose levels to cure diabetes

Chris - Now the pancreas that grew in the donor rat, was the tissue exclusively mouse tissue or were there other rat tissues in there? Because the thing is that although they stopped the pancreas forming they didn’t stop things like important structures like blood vessels from forming. So did they end up with mouse pancreas tissue with rat blood vessels in it?

Zhou - That is indeed the case. You are exactly right, the majority of the cells in the pancreas are derived from the donor mouse, but a minor fraction of the cells came from the rat host including blood vessels.

Chris - Is that not a consideration that when you transplant that tissue, were you to use a similar technique in a person say way in the future, you would potentially be transplanting animal blood vessel tissue with that organ, you might get a fairly vicious immune response against that foreign tissue which could destroy your donor tissue?

Zhou - Absolutely. That is a major concern. But what is surprising in this study is they have shown that if you use a relatively mild immunosuppressant to treat the recipient mouse for just a few days, that seems to be sufficient to suppress rejection.

Chris - What are the dangers of doing this kind of thing? If we are to see this come to fruition and we were to start using this as a source of spare parts for people, what could go wrong?

Zhou - The clear danger would be in the creation of the chimeric human animal. You don’t want a contribution of human cells into an animal’s system or even morphological features.

Chris - Are there risks from things like infection? Is there not a chance we could bring some additional infective cargo with it which could unleash some kind of problem for everybody afterwards?

Zhou - Yes. There has been a concern voiced for a long time and, for example, in the pig there are xenogeneic viruses that  can move around. But there are new technologies that are being applied, for example, by a group in Boston where they have been able to eliminate all all the xenogeneic viruses from the pig genome. So I think the technology is at the point where we can get a super clean animal that doesn’t have any viruses that could, potentially, be transmitted. I think that can be done technically and people have taken important steps in that direction.