The researchers cultured monkey embryos in the lab long enough to track the beginnings of organ formation and the development of the nervous system milestones that are difficult to observe in embryos growing in the womb.
The embryos reached an age of 25 days, making them possibly the oldest primate embryos to have grown outside the womb. Independent teams described the findings in separate papers1,2 in Cell on 11 May.
“It’s very impressive,” says Magdalena Zernicka-Goetz, a developmental biologist at the California Institute of Technology in Pasadena, who was not involved in the research. “It will bring a lot of new knowledge.”
Transition to 3D
Few things are as difficult as keeping lab-grown embryos alive for more than a few weeks most are nothing more than a jumbled bag of cells in a dish. Previously, both teams succeeded in cultivating monkey blastocysts spheres of dividing cells in Petri dishes for up to 20 days3,4. Beyond this point, all the embryos collapsed, so that more advanced stages of their development, such as early signs of the nervous system and organ formation, could not be seen.
But in the new studies, the researchers grew monkey embryos in small vials of culture medium, allowing the embryos to grow in three dimensions, as if they were in the womb. Both teams talked their embryos into surviving 25 days after fertilization.
Observing organs as they form
Hongmei Wang, a developmental biologist at the State Key Laboratory of Stem Cell and Reproductive Biology at the Chinese Academy of Sciences in Beijing, and her team obtained egg cells from female macaques (Macaca fascicularis) and fertilized them in the laboratory with sperm taken from their male counterparts.
A week later, they placed the resulting blastocysts in a gel-like mass in small cylindrical containers and watched them grow for 25 days.
Stem cell-derived “embryos” implanted into monkeys
By about two weeks after fertilization, more than half of the embryos had an embryonic disc—a flat mass of cells. These discs eventually formed the three main cell layers of the body: endoderm, mesoderm, and ectoderm. The lab-grown embryos also showed genetic traits similar to those seen in natural monkey embryos during the same time frame.
By day 20, the embryos have developed a neural plate one of the first hallmarks of the nervous system. As in natural embryos, this plate has thickened and bent into a tube that forms the base of the brain and spine. Wang and her team also pinpointed the cells that would eventually become motor neurons. Insights from lab-grown embryos will help researchers better understand early embryonic development in primates, Wang says.
In a second study, Tao Tan, a developmental biologist at Kunming University of Science and Technology in Yunnan, China, and his colleagues also created blastocysts from the eggs and sperm of cynomolgus monkeys. But they used two different types of cell culture to give the embryos stronger mechanical support and added glucose to give them energy as they grew.
As in Wang’s study, most of the cells in the cultured monkey embryos were of the same type as cells typically seen in natural embryos 18 to 25 days after fertilization. When Tan and colleagues took a closer look at the mesodermal cells of the embryos, they found that some differentiated into heart muscle cells and others matured into cells found in the lining of blood and lymph vessels. The team also pinpointed the cells that develop into connective tissue, which form the basis of the digestive system.
The researchers also found signs that blood cells and their components are beginning to form in the yolk sac, which supplies the embryos with nutrients. “We were deeply impressed,” says Tan. These blood cells “are nearly impossible to obtain during human embryonic development.”
Naomi Moris, a developmental biologist at the University of Cambridge in the UK, says the studies represent an important step in the development of methods that can keep embryos outside the womb for longer than previously possible. But he warns there is still a long way to go before lab-grown embryos look and behave like the real thing. “They still look a little different than how we would expect them to look at these stages,” says Moris, who was not involved in the research. “There’s definitely still room for improvement.”
Read Now:Taarak Mehta Ka Ooltah Chashmah’s Jennifer Mistry accuses Asit Modi of sexual harassment
