Millions of Human Cells Have Been Grown Inside Mice Embryos

Scientists have created millions of human cells in mouse embryos, in a technique which they hope could one day be used in a variety of ways, from growing organs for life-saving transplants to finding treatments for diseases including COVID-19.

The study centred around what are known as stem cells, which can grow into many different types of cells. Researchers at the State University of New York at Buffalo and Roswell Park Cancer Institute injected 10 to 12 human stem cells into 3.5-day-old mouse embryos.

After 17 days, millions of human cells formed in 10 mouse embryos. They included eye, liver, and red blood cells, which each represent one of the three types of cells we are made up of. The human cells accounted for between 0.1 to 4 percent of the cells in 14 of the mouse embryos, creating a chimera.

Professor Jian Feng of the Jacobs School of Medicine and Biomedical Sciences at State University of New York at Buffalo who co-authored the study published in Science Advances, told Newsweek: "This will enable the generation of human cells, tissues or even organs in animals."

Feng said he was most surprised that his team were able to produce lots of human red blood cells for reasons that are unclear. This shows that the human stem cells developed faster in the mouse embryos, as such cells would not be found in a human embryo until after about seven to eight weeks, he explained.

The study also showed how the team were able to turn stem cells from a primed to naïve state in order to grow the different cells. While naïve cells aren't on track to become a specific type of cell, primed stem cells are on the path to developing into a specific type of cell.

They did this by inhibiting an enzyme in primed human stem cells for three hours. This enabled the newly naïve human stem cells to grow with naïve mouse cells in the embryos. The technique previously used to create naïve human stem cells wasn't able to create human cells of different types in mouse embryos.

Feng said the technique could be used to produce mice which are better models of human diseases, "particularly infectious diseases that specifically or preferentially impact human, e.g., COVID-19.

"It is possible to make human immune cells or cells of the respiratory system in a mouse with this technology. Such chimeric mice would be very useful for studying COVID-19, which gravely impacts humans, but barely affects mice."

The method could also be used to generate organs in large farm animals, like pigs, for organ transplants in humans. But the approach would need to be significantly developed to translate what the team found in mice to large animals such as pigs, according to Feng.

"There are lots of hurdles to go through before it can be done. The human organs need to be free of pig cells. This would be very hard. One potential pathway is to understand how it works in a chimeric pig and try to develop an artificial system to grow human organs. If this can be realized, many patients who are waiting for organ transplant will be saved."

However, Feng acknowledged: "There are lots of things that we do not understand. More research is needed to understand how exactly human stem cells develop in a mouse embryo, whether it is possible to make even more human cells of a particular kind, for example, so the chimera can be used to study diseases or provide cells for transplantation. It is still at the early stage of this field."

Deborah Gumucio, Professor Emerita of the Department of Cell and Developmental Biology and Department of Internal Medicine at University of Michigan Medical School, who did not work on the project, told Newsweek: "This study's major advance is the establishment of culture conditions that permit the relatively (compared to previous studies) robust contribution of human embryonic stem cells to multiple organs/tissues in intact mouse embryos.

"This could eventually permit the study of human cells in the context of fully functioning organs, thereby offering real potential for new and exciting scientific exploration.

"A very surprising aspect to me was the amazing speed with which the human red cells and photoreceptors developed in the context of the mouse embryo. Of course, the functional properties of these human cells have yet to be examined.

"It makes one wonder, if we were to increase the amount of chimerism (maximally 4 percent in this study), would the developmental properties of the cells resemble those seen in mouse or human?" said Gumucio.

Although the work is an important proof of concept, Gumucio said: "In any groundbreaking study like this, tremendous potential sits side-by-side with limitations and questions that must be answered with further research.

"Here, the authors were able to achieve 0.14 to 4 percent chimerism. This might be enough to study the properties/behavior of the human cells in their new murine [mouse] homes, but, since we know that much of cell behavior is directed by cell to cell communication, will these cells behave like human cells or mouse cells?

"Certainly, the speed-up in development mentioned above suggests that the mouse environment does in fact affect human cellular development. Whether it also affects cell function will need to be further explored in each tissue/organ context."

Noa Novershtern of the Department of Molecular Genetics at the Weizmann Institute of Science, Israel, who didn't work on the study, told Newsweek: "As always, such exciting findings need to be repeated and confirmed by other labs. In addition, there is still a need to test carefully whether the human cells gained the function of the mouse tissue they reside in, as there is a possibility that they populate the embryo but do not function correctly."