27 January 2017

An important step towards xenotransplantology

Scientists have created an embryo with human and pig cells for the first time

RIA News

For the first time, an international group of geneticists has created full-fledged chimeric embryos in which pigs are combined with human and other mammalian cells. This opens the way for the cultivation of human organs in the body of animals, according to an article published in the journal Cell (Wu et al., Interspecies Chimerism with Mammalian Pluripotent Stem Cells).

"The work on this problem took four years. We clearly underestimated how much effort it would take to accomplish this task. This is an important first step towards growing human organs in a pig's body. Now we need to understand how to make human cells turn into the organs we need in order to realize our real task – to learn how to grow transplantable organs," said Juan Belmonte from the Salk Institute in La Jolla (in a press release, Scientists use stem cells to create human/pig chimera embryos – VM).

About 15 years ago, biologists began actively discussing the possibility of so–called xenotransplantation - the transplantation of animal organs into the human body. To bring this idea to life, as it seemed before, it was necessary to solve a simple task – to force the immune system not to reject other people's organs.

This task, as you might guess, has not yet been solved, although now geneticists are working on creating special gene therapies that make the organs of pigs and other animals invisible to our immune system. Only last year, the famous American geneticist George Church came close to solving this problem by removing some of the "friend-foe" labels using the CRISPR/Cas9 genomic editor.

Belmonte and his colleagues used the same system in order to approach the solution of this problem by the method of "from the opposite" – the creation of human organs for transplantation grown inside the pig's body. They can be created if human stem cells are introduced into the embryo of a pig or other animal during a strictly defined period of development, obtaining a so–called "chimera" - an organism composed of two or more sets of heterogeneous cells.

chimera.jpg

Such experiments, as scientists say, have been successfully conducted for a long time in experiments on mice, but experiments on large animals, such as pigs or monkeys, have not yet been conducted or ended unsuccessfully. Belmonte's team has made a big step towards the implementation of such tasks, having learned to insert virtually any cells into the embryos of pigs and mice using CRISPR/Cas9.

This DNA editor is used as a kind of "killer", selectively killing part of the cells in the embryo at the moment when one or another organ begins to form inside the embryo. At this moment, scientists introduce stem cells of another animal species into the nutrient medium, which fill an empty niche and begin to turn into the organ whose "blank" was destroyed with CRISPR/Cas9. Other tissues and organs are not affected, which is important for ethical reasons.

Having tested the work of this technique on mice by growing "rat" pancreas in their body, scientists spent almost four years adapting this technique to work with human and pig cells. The problem was that the pig embryo develops three times faster than its human counterpart, and Belmonte and his colleagues took a very long time to find the right time to implant human cells.

Having solved this problem, the scientists successfully replaced the future muscle cells in several dozen pig embryos, and implanted them back into the womb of their adoptive mothers. Approximately two-thirds of the embryos successfully developed for a month, after which the scientists had to stop the experiment for ethical reasons in accordance with US law.

Success in the implementation of this task, as Belmonte notes, opens the way for the real creation of full-fledged human organs ready for transplantation and not rejected by our body. Now Belmonte and his colleagues are working on adapting CRISPR/Cas9 to work in the pig's body, and obtaining all the necessary permits for such experiments.

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


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