An international group of scientists led by the Spaniard Juan Balmonte, known for his work in the field of stem cells, managed to create embryos of human and pig chimeras, which in the future may become a source of donor organs. Another team of researchers used viruses to treat congenital deafness in mice. "Lenta.ru" talks about the success of genetic engineering related to medicine.
The creation of genetically modified organisms is not the only way that genetic engineering can please humanity. Biotechnology makes it possible not only to change genes to improve agricultural plants and animals, but also to treat previously incurable diseases. Ironically, for this, scientists use the eternal enemies of man - viruses. The latter are used to create vectors that deliver DNA to the desired cells. Another direction that may frighten people who are not too knowledgeable in science is the creation of chimera embryos that combine cells of humans and other organisms. However, what seems sinister at first will actually prove to be a convenient way to create organs.
Kidneys or lungs that have been obtained by growing chimeric embryos will be suitable for transplantation to people in need. Those fearing a mutant uprising should think that the real benefits of this technology outweigh the vague fears of pessimistic science fiction writers.
From left to right: normal mouse, mouse with rat cages, rat with mouse cages, normal rat
Image: Nakauchi et al. / The University of Tokyo
To dispel fears, you need to understand what and how scientists who create chimeras are doing. The main material that researchers work with is stem cells, which have pluripotency - the ability to transform into other cells in the body (nerve, fat, muscle, and so on) with the exception of the placenta and yolk sac. They are introduced into the embryos of other organisms, after which the embryo develops further.
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Pigmen
This is how an international team of scientists from the United States, Spain and Japan managed to create the pig-man, rat-mouse and cow-man chimeras. They reported this in an article published in the journal Cell, which became the first document to support the successful "chimerization" of related species.
The main problem is that it is not enough to introduce pluripotent cells into the embryo and wait for something good to come out. Instead, it can end up with an organism with catastrophic developmental disabilities, including the formation of teratomas. It is necessary to turn off the genes in the recipient embryos so that they cannot form specific tissues. In this case, the implanted stem cells take on the task of growing the missing organ.
First, scientists injected rat stem cells into mouse embryos at the blastocyst stage, when the fetus is a ball of several dozen cells. This method is called embryo complementation. The aim of the experiment was to find out which factors play a leading role in interspecies chimerism. The embryos were transferred into the body of female mice, after which they developed into living chimeras, one of which survived until the age of two.
Genes in embryos were turned off using CRISPR / Cas9 technology, which makes breaks in specific regions of DNA. For example, the researchers, when testing their approach, blocked the activity of a gene that plays an important role in the formation of the pancreas. The mice that were born died as a result, but the missing organ developed when pluripotent rat cells were introduced into the embryos. Scientists also turned off the Nkx2.5 gene, without which the embryos suffered from serious heart defects and turned out to be underdeveloped. Chimerization helped the embryos achieve normal growth, however, no living chimeras were obtained.
Photo: Juan Carlos Izpisua Belmonte / Salk Institute for Biological Studies
A study of the resulting rat-mice showed that different mouse tissues contained a different proportion of rat cells. When scientists tried to inject rat cells into pig blastocysts and then performed genetic analysis of four-week-old embryos, they found no rodent DNA. This suggests that not all animals are suitable for chimerization with each other, and the successful grafting of stem cells from some embryos to others may depend on genetic, morphological or anatomical factors.
The main goal of the scientists was to create a chimera of a man and a pig, in order to trace how human tissues will develop inside the embryo of a non-ruminant cloven-hoofed animal. They used pig blastocysts and, using a laser beam, made microscopic holes for the subsequent injection of various groups of pluripotent cells, which were grown under different conditions. Then the embryos were transferred to sows, where they developed successfully. Tracking the dynamics of human material was carried out using a fluorescent protein, for the production of which human stem cells were programmed.
As a result, cells were formed in the porcine embryo, which are the precursors of various types of tissues, including the heart, liver and nervous system. The pig / human hybrids were allowed to develop for three to four weeks, after which they were destroyed for ethical reasons.
Deaf mice
American scientists from Boston were recently able to return hearing to mice suffering from a rare genetic disorder of inner ear function. To do this, they used a biological gene delivery system (vector) based on neutralized viruses. Researchers have modified an adeno-associated virus that infects humans but does not cause disease.
The infectious agent is able to penetrate hair cells - receptors of the auditory system and vestibular apparatus in animals. Biotechnologists have used the vector to repair the defective Ush1c gene in the cells of newly born live mice. This mutation causes deafness, blindness, and imbalance. As a result, the animals' hearing improved, which allowed them to distinguish even quiet sounds.
Genetic engineering, therefore, is not a way to create mutants that threaten humanity. This is a constantly improving set of methods and means to improve the life and health of people, especially those who are in great need of it. Since the creation of chimeras and gene therapy are not so easy to implement and sometimes require ingenious solutions, the development of biotechnology is not happening as quickly as we would like. However, dozens of scientific papers are published annually that deepen and enrich our knowledge and skills.
Alexander Enikeev
