New mouse and human embryo chimicos contain up to 4% of human cells

Beijing time on June 2, according tomedia reports, chimera generally refers to two groups of different sets of DNA composed of organisms. In a new study, scientists have developed mice-human chimeric embryos that contain up to 4% of human cells, the largest number of human cells of any chimeric to date.

New mouse and human embryo chimicos contain up to 4% of human cells

  This is a mouse-human chimeric that shows human cells (green) in 17-day-old mouse embryos (blue), mainly red blood cells that accumulate in the liver of mice

Surprisingly, these human cells can even learn from mouse cells and develop faster, in other words, the chimeric embryo is closer to the rate at which mouse embryos develop than to the slower human embryos. Jane Feng, a professor of physiology and biophysics at the State University of New York at Buffalo and one of the study’s authors, said the finding was “very accidental . . . We didn’t actually foresee that.”

Successfully growing human cells in mouse embryos could one day help scientists understand the growth and aging process of the human body, or explore how diseases such as COVID-19 can damage cells, and these chimeric embryos could eventually be used as stents to grow transplanted organs, Professor Feng said.

Professor Feng’s team solved a long-standing problem in the cultivation of such chimerics: How do they do this in order for human and mouse embryonic stem cells to be able to communicate and mix with each other? Embryonic stem cells are versatile and can develop into any type of cell in the body.

But, Professor Feng points out, “human embryonic stem cells look and behave very differently from mouse embryonic stem cells”, so past attempts to fuse them have failed. At first, the researchers thought the failure was due to a species barrier, but after years of research, they realized that it was not a species problem, but a maturity problem.

Human stem cells are at a later stage of development, known as “primed”, and usually occur only after human embryos have been implanted into the uterine wall. In contrast, mouse stem cells are in a “naive state”, which usually occurs when mouse embryos are still floating in the fallopian tubes. Professor Feng said that in the past researchers were unable to convert human cells back to their original state.

Bring the human cells back to their original state.

New mouse and human embryo chimicos contain up to 4% of human cells

Human cells formed in the eyes (blue) of mouse embryos (green)

In the experiment, Professor Feng and his team were inspired by the phenomenon of “embryonic dapause”, which has been found in hundreds of mammals, from mice to bears. When difficult situations occur, such as famine or lack of water, some animal embryos can remain in their mother’s fallopian tubes for months, sometimes more than a year, until environmental conditions improve.

It’s not clear what triggered the embryo’s development already stagnant in its primitive state, but a protein called mTOR appears to act as a sensor that can detect when environmental conditions are bad. His team found that they could target the protein in human stem cells, making cells think they are experiencing famine and need to “jump” to a more “primitive” state to preserve energy.

MTOR usually promotes the production of proteins and other molecules to support cell growth and proliferation, so by inhibiting mTOR, Professor Feng’s team successfully induced human stem cells, altering their metabolism and gene expression, causing them to reverse from the origin state to the primitive state. “So these cells behave like mouse cells, ” says Professor Feng. So the researchers were given a set of primitive human stem cells that could be cultured with mouse stem cells and “well mixed together.” The researchers then injected 10 to 12 primitive human stem cells into mouse embryos.

In most mouse embryos, primitive human stem cells have successfully developed into mature human cells in all three embryo layers. The three embryo layers are: the outer embryo layer, i.e. the primary cell layer developed as the embryo grows, which later develops into hair, nails, epidermis and nerve tissue; However, without the spread of human cells to the reproductive cell tissue, the tissue subsequently develops egg and sperm cells.

The three embryos then develop into more differentiated cells. When the researchers stopped the experiment on the 17th day, 14 embryos had human cell content ranging from 0.1% to 4%, and human cells, including liver, heart, retinal and red blood cells, were found in each part of the embryo.

What really “surprises” human cells, however, is the speed at which they develop. For example, these embryos can produce human red blood cells within 17 days, while in normally developed human embryos, red blood cells take about 56 days to develop. Similarly, eye cells in human embryos do not develop until very late, while chimeric embryos can develop human eye cells, including photosensitive cells, within 17 days. Professor Feng said human cells “show the biological clock of mouse embryos”. Previously, scientists thought this accelerated development was impossible because the rate at which human cells develop edified has long been considered “unalterable.”

Organ Transplantation and Moral Dilemma

The new study, which established a “new method” that could transform induced human pluripotent stem cells into primitive states, has a lower level of chimeric than another study that contains up to 20 percent of human cells per embryo, but the study was published May 24 in biorxiv, a preprint database, and has not yet been peer-reviewed. In summary, these studies provide a new perspective for acquiring multi-functionality in vitro and highlight barriers to successful interspecies integration, and finding ways to overcome them may contribute to the development of regenerative medicine.

These findings may “stimulate research into basic understanding of human development,” especially the time differences involved in biological systems. This chimeric can also help scientists understand human diseases. For example, researchers may one day be able to regenerate human blood in mouse models and study diseases such as malaria. If human lung cells or respiratory epithelial cells can be created, mice could become “model systems” for studying diseases such as new coronary pneumonia. In other words, you can infect new coronary pneumonia with mice that carry human cells, and then learn how the virus attacks human cells.

The most commonly mentioned potential application of this type of chimeric is the incubation of organs, but this may not happen in mice, but in larger animals such as pigs. Of course, these applications also raise ethical questions. One ethical consideration is that chimers blur the boundaries between species, making it difficult to determine the morality or awareness these animals possess. For example, according to previous studies, the chimerics used in animal experiments may have been given too many human characteristics and have a similar moral status or consciousness to us.

There is still a lot of discussion before considering such applications. Carol Ware, associate director of the Institute of Stem Cell and Regenerative Medicine at the University of Washington, who was not involved in the new study, said more exploration was needed before the field became a reality. Several of the main obstacles are the identification of the host species of these human cells and the public’s acceptance of the work.

“At the moment, the pace at which this clinical opportunity becomes a reality does not seem to be hindered by the ability of human organs to grow,” adds Carol Weir. She would like to see if these primitive human cells can develop again when the mTOR protein is removed from a laboratory dish, especially if some key cellular processes can be restored. Professor Feng’s team’s findings were published May 13 in the journal Science Advances. (Any day)