Human-mouse chimeras have been created in recent research, in which scientists report the development of intestines, livers, and even brains within mice containing human cells.
The novel research, discussed on June 12 at the International Society for Stem Cell Research meeting in Hong Kong, involves injecting human cells into the amniotic fluid of pregnant mice. The research has not yet undergone peer review.
Hideki Masaki, a stem-cell scientist at the Institute of Science Tokyo who attended the meeting, called the work “game changing,” although the researchers say that to become practically useful, their work will need to increase the ratio of human to mouse cells.
Understanding Chimeras
Named after the mythical Greek creature composed of parts from several animals, real-world chimeras are organisms with more than one cellular genotype. These can arise through natural or artificial means, such as embryo fusion, organ transplants, or plant grafting.
Laboratory-made human–animal chimeras are typically created by introducing human cells into mouse or pig embryos in a dish, rather than in a living animal’s womb. In most past experiments, human cells have struggled to survive under such conditions, and researchers have lacked the ability to control what types of differentiated cells emerge from the stem cells. While these experiments have provided insights into tissue development, the ultimate goal of growing full human organs for transplantation remains out of reach.
A research team—including University of Texas MD Anderson Cancer Center biomedical engineer Xiling Shen and Terasaki Institute for Biomedical Innovation developmental biologist Qiang Huang—focused on two major challenges: improving the survivability of human cells and controlling which organs they target.
Their hypothesis was that using organoids—three-dimensional human tissue models grown from more mature cells—would yield better results than early-stage stem cells, making them more resilient in a foreign environment.
First, the scientists programmed the cells to develop into gut, liver, and brain organoids in a lab dish. They then injected these organoids into the amniotic fluid of mice at an early stage of embryonic development, allowing the pregnancies to continue to term.
Inspecting the Results
“It’s a crazy experiment; I didn’t expect anything,” said Shen. “You get sections of the intestine that originate from injected human organoids.”
The results were evident within days, as the human cells in the amniotic fluid entered the embryos, located their target organs, and began to multiply. Each organoid sought out its intended destination—including the liver, intestines, and cortex. After birth, about 10% of the mice had human cells in their intestines, comprising roughly 1% of the intestinal cells. Human cells were also found in the brains and livers, though to a lesser extent.
Most notably, the human cells appeared to function normally and remained alive two months after the mice were born. When the team examined the liver tissue, they identified cells producing the human version of albumin, a key liver protein. The foreign cells appeared to be stable—a promising outcome for future applications.
Ethical Concerns
Injecting cells into the amniotic fluid represents a major step toward making chimera creation more viable and controlled. Attendees such as Stanford researcher Hiromitsu Nakauchi praised the work, with Nakauchi noting he may adopt the method in future research. Still, the team acknowledges that much more progress is needed to improve the number of viable human cells integrated into the developing embryos.
Ethicists continue to raise concerns about the implications of animals developing human brain cells—and the potential for human-like cognition. The researchers behind this study say the number of human cells found in the mouse brains is too low to warrant such fears at present, but acknowledge the ethical debate may intensify as the field advances.
Ryan Whalen covers science and technology for The Debrief. He holds an MA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org, and follow him on Twitter @mdntwvlf.