Blurring the Lines? Researchers Create Human-Pig Chimera Embryos

In Greek mythology, the chimera was a fire-breathing she-monster made of more than one animal (lion, goat, and snake). In modern biology, chimeras are embryos that contain cells from another species.

Researchers from the Salk Institute (La Jolla, California) have grown human stem cells in early-stage pig embryos. The report, published January 26 in Cell, is the first account of a human—pig chimera precursor. The research group also performed a proof-of-concept study with rat­–mouse chimeras.

“Our findings may offer hope for advancing science and medicine by providing an unprecedented ability to study early embryo development and organ formation, as well as a potential new avenue for medical therapies,” said senior author Juan Carlos Izpisua Belmonte, PhD, on the Salk Institute website.

Investigators hope that chimera research will lead to new models of human disease and new methods of drug testing. The ultimate goal, they say, is to grow transplantable human organs with a much lower risk of rejection because they would be developed from a patient’s own cells (stem cells derived from the patient’s skin cells).

In the proof-of-concept study, the research group showed that organs from one species could be grown in an animal of another species. They inserted rat stem cells into mouse blastocysts and implanted the resulting chimera embryos into mouse mothers. Some of the chimeras survived to adulthood, with the rat cells contributing to many mouse tissues—including the gallbladder, which rats lack—but not evidently affecting the overall appearance or life span of the mouse. To direct the stem cells to form a specific organ, they used gene editing to create a line of mice lacking genes necessary for pancreas development. Without a pancreas, these mice could not survive long. However, after being injected with rat stem cells containing the missing pancreas-encoding genes, mouse embryos did develop functioning pancreases, and some survived to adulthood.

Because rodents are too small and developmentally different from humans to grow human tissue, the investigators chose pig embryos to test the types of human stem cells best suited for cross-species implantation. They found that human—pig chimera embryos could develop from naive and intermediate pluripotent stem cells (of earlier developmental origin than primed pluripotent stem cells). However, the efficiency was low.

They transferred the chimera embryos into surrogate sows and allowed them to grow for 21 to 28 days, at which point they stopped the experiment to avoid the ethical problem of creating mature chimeras. More than half of the embryos had stunted growth at this point compared with controls, showing that the presence of human stem cells may have interfered with normal development of the pig embryos.

This study is only a first step, say the investigators, noting that their procedures can improve the understanding of embryo development. “Ultimately, these observations also raise the possibility of xeno-generating transplantable human tissues and organs towards addressing the worldwide shortage of organ donors,” they write.

Dr. Laurie Anne Walden received her doctorate in veterinary medicine from North Carolina State University. After an internship in small animal medicine and surgery at Auburn University, she returned to North Carolina, where she has been in small animal primary care practice for over 20 years. Dr. Walden is also a board-certified editor in the life sciences and owner of Walden Medical Writing, LLC. She works as a full-time freelance medical writer and editor and continues to see patients a few days each month.