Scientists have made the most thoroughly-integrated mouse-human hybrid that is a lot mouse and a little bit human. Researchers reported on May 13 in Science Advances that human stem cells can knit themselves into growing mouse embryos with a bit of help, complete with a developing liver, heart, retina, and blood.
Usually, finicky human cells do not tend to grow well in other animals, but the scientists found in one of the new embryos that 4% of its cells were human. They describe this hybrid of mouse-human as the most thorough mixing between human and mouse yet.
Stem cell and development biologist, Juan Carlos Izpisua Belmonte, from the Salk Institute for Biological Studies in La Jolla, Calif, said that the level of integration is quite striking and if other scientists can replicate the findings, "it potentially represents a major advance." Izpisua Belmonte is not involved in the study.
Chimeras: Organisms Engineered to Have Cells of Multiple Animals
Chimeras are single organisms made up of cells from two or more "individuals," containing two sets of DNA with the code to make two separate organisms.
The new mouse-human hybrid that the scientists developed could reveal how a single cell can give rise to an entire organism. Additionally, this could also prove valuable in studying diseases that affect more people than animals. Chimeras could ultimately become a source of human organs with the help of more advanced technologies, Science News reports.
Stem cell and developmental biologist, Jun Wu from the University of Texas Southwestern Medical Center in Dallas, and not involved in the study, said that they had analyzed thousands of embryos but never saw robust chimeric contribution of human stem cells to mouse embryos beyond day 12.
The success of this new method all comes down to timing, said Jian Feng, a neuroscientist and stem cell biologist of University at Buffalo in New York. Developmental clocks of human stem cells must be turned back to an earlier phase called the naïve stage to grow and thrive in a mouse embryo.
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How Did They Do It?
According to Feng and his colleagues, by silencing a protein called mTOR for three hours, the developmental clocks of the stem cells were reset to an earlier stage. Presumably, the brief treatment shocked the cells back to their naïve stage restoring their ability to turn into any cell in the body.
Ten to twelve batches of these more youthful human stem cells were injected into the mouse embryos, with about 60 to 80 mouse cells. The team of researchers then allowed it to develop for 17 days.
The outward appearance of the embryos grew normally despite having human cells. The researchers found that these embryos have human cells about 0.1% to 4% of the total cells in the embryos after tallying the DNA specific to either human or mouse.
Destined to become the liver, heart, bone marrow, and blood, human stem cells knitted themselves into most developing of the mouse. In particular, researchers found that human red blood cells are abundant in these mouse embryos.
A small amount of human cells was also discovered in the tissue that will soon form the brain, while another embryo had numerous photoreceptors, eye cells use for detecting light. As far as the scientist could tell, no human cells are found to go on to develop sperm and egg.
The normal sluggish developmental pace of human cells sped up to match their host once they are inside it. In 17 days, scientists were able to have mature cells that would otherwise take months to get in a normal human embryo.
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