Mouse pancreas in rat body: details

Cradle for the pancreas

Kirill Stasevich "Science and Life"

The hormone insulin is synthesized by special cells of the pancreas. If they die for some reason, type I diabetes begins: due to a lack of insulin, our organs and tissues cannot properly absorb glucose, blood sugar levels rise, and serious health problems develop following a disturbed metabolism. And even if we eliminate the reason why the insulin cells died, they need to be restored somehow.

It goes without saying that they can be transplanted, either together with the whole pancreas, or only these cells themselves, which form characteristic clusters in the gland called islets of Langerhans. However, as with any transplantation, two problems inevitably arise here: firstly, a donor is needed, and secondly, you need to be constantly ready for rejection of the transplanted tissue. Rejection is usually fought by suppressing the activity of the immune system with special drugs, but here you have to be prepared for the fact that the "sleepy" immune system will miss an infection or cancer.

Rejection problems could be avoided if the transplanted organ or cells genetically matched the organism into which they are transplanted. Where to get such a "second copy"? Obviously, stem cells are needed here, and not natural embryonic ones, but induced ones, which are obtained artificially by reprogramming some mature, specialized cells. For example, taking skin cells from a patient, they can be reprogrammed into stem cells, so that later they can grow an organ or tissue to replace the damaged one. However, in many cases it is impossible to do what is required, just on the laboratory table – in order for an organ or its fragment to form as it should, it must develop in a natural environment, that is, in the whole organism.

Some time ago, researchers from the University of Tokyo, together with colleagues from Stanford, managed to grow a rat pancreas in a mouse: mouse stem cells were transplanted into rats, after which an organ grew inside the rats, which was mouse by genetics (see the press release Rat-grown mouse pancreases help reverse diabetes in mice). But how was it possible to avoid rejection? The fact is that the immune system in the course of embryonic development needs time to learn to distinguish "their" from "strangers". Stem cells were transplanted to rat embryos whose immunity was still developing – everything that the immune system "saw" around itself in the embryo, it considered "its own", and foreign stem cells, from which the pancreas was then obtained, also became "its own" for it.

As a result, the iron turned out to be rat in everything except size – it was mouse in size, and there were not enough insulin cells in it to completely make up for their shortage in a rat with diabetes. Then the researchers switched the animal roles, and in the same way they grew a mouse pancreas in a rat. The rats were modified so that their own pancreas did not form and did not interfere with the one that would grow from mouse stem cells. As a result, rats received a gland that genetically corresponded to mice, but at the same time was rat–sized - that is, there was more than enough material for transplantation in it.

Drawing from an article in Nature – VM

An article in Nature (Yamaguchi et al., Interspecies organogenesis generates autologous functional islets) states that after transplanting clusters of insulin cells (and more than a hundred such clusters were transplanted) to mice with diabetes, their blood sugar levels returned to normal and remained normal for 370 days. Since rat cells somehow got into the mouse body during transplantation, the mice were given immunosuppressants five days after the operation so that the immunity, which inevitably had to react to "strangers", did not get out of control. However, then the immunosuppressants stopped giving, and no rejection happened. When the insulin islets of Langerhans were extracted for analysis at the end of the experiment, there were no rat cells there: the immune system ate them out, and, having completed its task, calmed down – there was no reason for it to attack the insulin cells themselves, since they did not differ genetically from the mouse itself.

Usually, when it comes to manipulations with stem cells, they certainly mention the danger of cancer: if such a cell deteriorates, it can easily begin to form a malignant tumor. However, in this case, there were no signs of oncological processes in mice – probably because iron and insulin cells developed in an embryo (albeit rat), that is, in a more suitable environment for them.

So, as we can see, in principle, representatives of another biological species can be used for growing organs in general. Is it possible to do the same procedure with human cells and, for example, with a pig or a sheep? Probably, it is quite realistic: by introducing human stem cells into a pig embryo, we will get excellent material for transplantation, which will not irritate our immune system. However, before such a method enters medical practice, here, in addition to many necessary experiments, it will also be necessary to settle a number of ethical issues, which, of course, someone will inevitably have. 

Portal "Eternal youth" http://vechnayamolodost.ru 27.01.2017