An international team of scientists led by biochemist Juan Carlos Izpisúa has created chimeric macaque and human embryos for the first time, injecting human stem cells into primate embryos. “This work can help us better understand early human development and evolution, as well as provide a platform for disease modeling, drug development and the generation of transplantable human cells, tissues and organs,” explained the Spanish researcher to this newspaper from his laboratory at the Salk Institute, in La Jolla (California).
In Greek mythology, Chimera was a fabulous being that had the head of a lion, the body of a goat, and the tail of a dragon. In science, organisms generated in the laboratory by mixing genetic material from two or more species are called chimeras. Izpisúa and his collaborators explain in the journal ‘Cell’ that they have succeeded in integrating human stem cells into macaque embryos in their early stages of development, when there are around a hundred cells. ‘Human cells survived, proliferated and generated various post-implantation cell lines in monkey embryos. We have also discovered signaling events underlying the cross-species dialogue ”, indicates the Spanish biochemist, who had previously achieved rat and mouse chimeras.
The researchers, including Chinese scientists and from the Catholic University of Murcia, injected 25 human cells into each macaque embryo during its sixth day of development. These were pluripotent stem cells capable of generating most of the tissues and obtained from the reprogramming of adult cells. After one day, they detected human cells in 32 embryos, and after 10, 103 chimeras were still developing. From that moment on, survival took a spin and, on the nineteenth day – when the experiment ended – only three embryos survived.
Communication between species
“It is very difficult to keep chimeric cells alive in the laboratory even for a few days,” says Izpisúa, who adds that his work does not seek to create hybrid human and macaque individuals. ‘We are trying to understand how human cells communicate in the early stages after fertilization of an egg, which is not something we scientists can easily study otherwise. Studying how human cells communicate in a blastocyst, a ball of about one hundred cells, is a powerful method for understanding genes and other factors involved in cell development.
Four years ago, Izpisúa managed to integrate human cells into pig embryos and, now, he has also managed to communicate the macaque and human cells. The scientist says that, in the case of the human being and the pig, it is like trying to find common ground between the Chinese and French languages, while in that of the human and the macaque it is like doing it between Spanish and French. “Understanding which pathways are involved in chimeric cell communication will possibly allow us to improve this communication and increase the efficiency of chimerism in a host species that is evolutionarily more distant from humans,” he points out in reference to the pig.
The WHO, recalls the Salk Institute in a statement, estimates that the 130,000 organ transplants performed each year represent only 10% of those that would be necessary due, in large part, to the shortage of organs. The Spanish biochemist trusts that the knowledge acquired with this line of research will allow in the future «to generate human cells and tissues in an evolutionarily more distant species (from us than the monkey) such as the pig, which for various reasons, including social ones, economic and ethical, it might be more appropriate overall for regenerative medicine therapies. ‘ That is, using pigs to grow human organs for transplantation.
Furthermore, “since we cannot perform certain types of experiments on humans, it is essential that we have better models to study and understand human biology and disease more precisely. An important objective of experimental biology is the development of models that allow the study of human diseases under ‘in vivo’ conditions ”, says the biochemist.