Researchers in China and the United States injected human stem cells into primate embryos and were able to grow chimeric embryos for a significant period of time – up to 20 days. Research, despite its ethical concerns, has the potential to provide new insights into the biology and evolution of development. It also has implications for the development of new models of human biology and disease. The work appears on April 15 in the review Cell.
“As we are unable to conduct certain types of experiments in humans, it is essential that we have better models to study and understand human biology and disease more precisely,” says lead author Juan Carlos Izpisua Belmonte, professor in the Gene Expression Laboratory at the Salk Institute for Biological Sciences. “An important goal of experimental biology is the development of model systems that allow the study of human disease under in vivo conditions.”
Interspecific chimeras in mammals have been manufactured since the 1970s, when they were generated in rodents and used to study early developmental processes. The breakthrough that made the current study possible came last year when the collaborative study team – led by Weizhi Ji from Kunming University of Science and Technology in Yunnan, China – generated a technology that allowed monkey embryos to stay alive and develop outside the body for an extended period of time.
In the current study, six days after the creation of the monkey embryos, each was injected with 25 human cells. The cells came from an induced pluripotent cell line known as extended pluripotent stem cells, which have the potential to contribute to embryonic and extraembryonic tissues. After one day, human cells were detected in 132 embryos. After 10 days, 103 of the chimeric embryos were still developing. Survival quickly began to decline, and by day 19, only three chimeras were still alive. But it’s important to note that the percentage of human cells in embryos has remained high throughout their growth.
“Historically, the generation of human-animal chimeras has suffered from the low efficiency and integration of human cells into the host species,” says Izpisua Belmonte. “The generation of a chimera between human and non-human primates, a species more closely related to humans along the evolutionary timeline than any previously used species, will allow us to better understand if there are any imposed barriers. by evolution to the generation of chimeras and if there are any means by which we can overcome them. “
The researchers performed a transcriptome analysis on human cells and monkey embryos. “From these analyzes, several communication pathways that were either new or enhanced in chimeric cells were identified,” says Izpisua Belmonte. “Understanding which pathways are involved in the communication of chimeric cells will eventually allow us to improve this communication and increase the efficiency of chimerism in a host species that is further removed from human evolution.”
An important next step for this research is to further assess all of the molecular pathways involved in this interspecies communication, with the immediate aim of finding which pathways are vital for the developmental process. In the longer term, the researchers hope to use the chimeras not only to study early human development and to model disease, but also to develop new approaches for drug screening, as well as potentially generating cells, tissues or cells. transplantable organs.
An overview of support in Cell presents the potential ethical considerations surrounding the generation of human / non-human primate chimeras. Izpisua Belmonte also notes that “it is our responsibility as scientists to conduct our research in a thoughtful manner, following all ethical, legal and social guidelines in place”. He adds that before starting this work, “consultations and ethical reviews were carried out both at the institutional level and through outreach to unaffiliated bioethicists. This thorough and detailed process helped guide our experiments.”
This work was supported by the National Key Research and Development Program, the National Natural Science Foundation of China, the Major Basic Research Project of Science and Technology of Yunnan, Key Projects of Basic Research Program in Yunnan Province, High-level Talent Cultivation Support Plan of Basic research projects of Yunnan Province and Yunnan, UCAM and Moxie Foundation.
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