Scientists have successfully generated millions of mature human cells in a mouse embryo, paving the preliminary road for future stem cell treatments capable of one day targeting chronic diseases through the potential replacement of damaged cells with healthy human cells or tissues.
"This is fundamental research that allows us to use the mouse embryo to help us better understand human development," said study author Jian Feng, PhD and professor of physiology and biophysics in a statement.
"Further development of our technology could enable the generation of even larger quantities of specific types of mature human cells to allow us to create more effective mouse models to study diseases that gravely affect humans, such as malaria or Covid-19.”
Previous attempts at producing human cells in vivo – or within a mouse embryo – have proven difficult due to the different properties and development speeds between mouse embryonic and human stem cells. Furthermore, human stem cells grown in a petri dish do not behave the same way as those in a body, which has in some ways stunted stem cell development in its potential ability to fight diseases.
Writing in Science Advances, researchers at the University of Buffalo successfully found a way to manipulate human pluripotent stem cells to “shock” them to an earlier and less developed state in what is known as a “naïve state.” This conversion allows the human stem cells to differentiate into various types of cells into the body so that one form is compatible with inner cell mass inside mouse blastocyst, triggering a series of events that “rewire gene expression and cellular metabolism.” Between 10 and 12 naïve human stem cells were injected into a 3.5-day-old mouse embryo. This manipulated compatibility allowed for the human stem cells to accelerate quickly enough to develop at the same pace as that of the mouse host. (For example, under normal circumstances the eye cells in a human embryo would develop at a much later stage.)
In just 17 days, millions of mature human cells were produced within the mouse embryo, making up about 4 percent of the total number of cells counted within the mouse embryos. However, the researchers advise that this is likely a “low estimate” because mature human red blood cells do not have a nucleus, making it difficult to count the total amount of generated red blood cells.
"We have a lot of questions to answer before the technology can be useful, but this is the first time that anyone has generated so many mature human cells in a mouse embryo," said Feng. In addition to generating material to treat critical diseases like diabetes or kidney failure, the researchers write that their findings may provide better, new abilities to model infectious diseases such as Covid-19. The respiratory disease has been shown to hardly affect mice and may serve as a possible avenue for creating a mouse model of the human immune system.
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