[Animal experiment]-"Human sheep embryos" were successfully cultivated, and the cultivation of human organs with other animals will go further

  As researchers announced the successful breeding of sheep embryos containing human cells, sci-fi scenes depicting the cultivation of human organs in other animals have gradually become reality.

  Scientists claim that cultivating human organs in animals can not only increase the supply of organs, but also use gene editing technology to make organs more compatible with the immune systems of transplant recipients. If the patient’s own cells are used for culture, the possibility of rejection can even be completely eliminated.

  According to data from the Department of Blood and Transplantation of the National Health Service (NHS) in the United Kingdom, in 2016, about 460 patients died while waiting for their organs. At the same time, some patients who received transplants also experienced organ rejection.

  "Until now, the most matched organs, except for those from identical twins, have been unable to maintain their function for a long time due to the continuous attack of the immune system." From the University of California, Davis, dedicated to making human organs other than Said Dr. Pablo Ross, a member of the research team on the growth of species in vivo.

  Ross added that if human organs can grow in other species, then organ transplantation technology may be able to bring people back to life.

  Bruce Whitelaw, a professor of animal biotechnology at the Roslin Institute, the birthplace of Dolly the Sheep, said that although there is still a long way to go before the goal of truly cultivating human organs in other animals, the current The latest research "is a major step in starting to explore whether sheep can be used as a supply species for this magnificent'chimeric' project."

  Currently, xenotransplantation of organs from another species directly to humans is still a feasible way for humans to solve the shortage of organs. However, the rejection reaction caused by this method is still a serious problem that medical personnel must face.

  Because of this, scientists have been trying to cultivate organs of one species in another species: After hard work, scientists have successfully cultivated rat pancreas in mice.

  But recently, Ross and his colleagues have made an important breakthrough in us humans: they have been able to implant human stem cells into early pig embryos, and about 1 in 100,000 pig cells will be human cells. However, due to regulations, these chimeras are only allowed to develop for 28 days.

  Today, at the recent American Conference for the Advancement of Science in Austin, Texas, the research team announced that they have created a similar sheep embryo with a higher ratio of human/animal cells. "One out of every 10,000 cells in these sheep embryos is a human cell," Ross said.

  The research team said that they have been able to use gene editing technology to create pig embryos and sheep embryos that cannot develop pancreas. The next step will focus on the problem of pancreas development. They hope that the human cells implanted in such embryos can grow normally and replace the missing organs.

  The research team is currently only allowed to grow chimeric embryos for up to 28 days, while chimeric sheep embryos are allowed to grow up to 21 days. Although it may be enough to observe the development of missing organs after human cells implanted in gene-edited embryos, the research team member, Dr. Hiro Nakauchi from Stanford University, said that an experimental period of about 70 days would be more convincing, but this Additional approval from the institutional review board is required.

  However, Ross said that if this method is used, the human/animal cell ratio should be at least 1%, instead of the current one in 10,000, which means that a lot of work still needs to be done to make human cells in a chimera. The proportion within has increased.

  Ross added several advantages of using sheep embryos, including that they can be bred using simple in vitro fertilization techniques and require fewer embryos to be implanted into the uterus of adult sheep, which means that the entire experiment requires more embryos. less.

  "We generally implant 50 embryos into each recipient pig," Ross said. "To the sheep we only need 4 embryos per recipient."

  Sheep, like us, have organs with well-defined functions, such as the heart and lungs, and experiments have shown that their embryos can be chimerized with goat embryos to give birth to "mountain sheep." Like pigs, sheep’s organ sizes are suitable for humans.

  Research on pigs is still ongoing. Ross said that they have noticed that pigs have other advantages, including development speed and more pups per birth, which means fewer animals can produce more experimental data.

  However, ethical concerns abound. For example, whether chimeras can develop brains and thoughts like humans is worth worrying about.

  "I have the same concerns," Ross said, for which the research team is focusing on the final development direction of human cells in the chimera. "If our experimental results show that human cells will eventually produce animal brains, we will never continue to study." He said.

  Nakauchi is optimistic that humans will eventually be able to obtain organs developed from animals. "It may take 5 years or even 10 years, but I firmly believe that in the end we will do it," he said.

  Nakauchi also believes that those concerns expressed are not important: “Currently, there are very few human cells. It is impossible to produce pigs with human faces or human brains,” he said. "We have published several articles showing that we have the ability to target the target area, so we can prevent human cells from differentiating into the brain or gonads."

  Other potential problems include that the DNA of the virus in animals may infect human cells, and that human organs may have blood vessels made up of host animal cells. "Once such an organ is transplanted into the human body, it will cause a rejection reaction of the immune system-it is likely to be a hyperacute rejection reaction," said Stem Cell Biology and Development from the Francis Crick Institute in the United Kingdom Said Robin Lovell-Badge, head of the genetics department.

  However, recent advances in gene editing technology have made it possible for scientists to obtain virus-free piglets, paving the way for such studies to a certain extent. At the same time, Ross pointed out that human cells may be able to replace the remaining after organ transplantation. Host animal cells.

  Recently, the National Institutes of Health suspended funding for this research. However, through a series of review processes, the suspension may be cancelled. Scientists in the UK must apply to the Home Office for permission to conduct such research.