AsianScientist (Apr. 20, 2021) – In a world first, researchers from China and the United States have grown human-monkey chimeric embryos that lived up to 20 days—a significant milestone in the rapidly advancing field of developmental biology. Their work was published in Cell.
While the concept of a chimera—a fearsome beast with a lion’s head, goat’s body and dragon’s tail—dates back to ancient Greece, modern-day chimeras are much less monstrous. In the 1970s, chimeras with cells of two or more species were generated in rodents to trace cell lineage in early development.
Beyond embryology, chimeras can also serve as models to accurately study and understand human biology and disease—especially when certain experiments cannot be ethically or feasibly conducted in humans. Despite their promise, efforts to create human-animal chimeras have proven difficult over the years.
“Historically, the generation of human-animal chimeras has suffered from low efficiency and integration of human cells into the host species,” said senior author Professor Juan Carlos Izpisua Belmonte from the Salk Institute for Biological Sciences.
Enter the team of Professor Ji Weizhi from the Kunming University of Science and Technology. In 2020, Ji and his colleagues made waves by developing technology that allowed monkey embryos to stay alive and grow outside the body for an extended period of time. As humans and monkeys are closely related, Ji’s technology could help bring human-animal chimeras closer to reality.
True enough, it did. With the two institutes joining forces, the combined China-US team injected 132 six-day old cynomolgus monkey (Macaca fascicularis) embryos with 25 human extended pluripotent stem cells (ESCs). As suggested by their name, ESCs can grow into various cell types even outside an embryo.
Human cells were detected in all embryos after one day, with 103 of the chimeric embryos still developing after ten days. However, the embryos soon deteriorated: at 11 days after fertilization, 91 were alive, and by day 19, only three living chimeras were left.
Notably, the percentage of human cells in the chimeric embryos remained high throughout their short lifespan. By performing transcriptome analysis on the human and monkey cells from the embryo, the researchers identified several pathways involved in communication between the two cell types.
While their study has sparked considerable ethical debate, the team hopes to further flesh out all the molecular pathways involved in interspecies communication. In the long run, they envision the chimeras being used not just for developmental studies or disease modeling, but also for drug screening and the generation of transplantable cells, tissues or organs.
“Generation of a chimera between human and non-human primate will allow us to gain better insight into whether there are evolutionarily imposed barriers to chimera generation,” concluded Belmonte. “Understanding which pathways are involved in chimeric cell communication will allow us to possibly enhance this communication and increase the efficiency of chimerism in a host species that’s more evolutionarily distant to humans.”
The article can be found at: Tan et al. (2021) Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo.
Source: Kunming University of Science and Technology.
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