Scientists have created a model human embryo with a heartbeat and traces of blood in an advance that offers an extraordinary window into the first weeks of life.
The synthetic structure, created from human stem cells without the need for eggs, sperm or fertilisation, replicated some of the cells and structures that would typically appear in the third and fourth week of pregnancy. But it was specifically designed to lack the tissues that go on to form the placenta and yolk sac in a natural embryo, meaning that it did not have the theoretical potential of developing into a foetus.
Despite the resonance of a heartbeat, this safeguard makes the experiments ethically uncontroversial, the team behind the work argue – a view supported by international guidelines.
“I’d like to emphasise that these are neither embryos nor are we trying to make embryos actually,” Dr Jitesh Neupane, of the University of Cambridge’s Gurdon Institute, told the International Society for Stem Cell Research’s annual meeting in Boston on Saturday. “They are just models that could be used to look into specific aspects of human development.”
Nonetheless, the first glimpse of the pulsating cells under the microscope was a profound experience, Neupane said.
“I randomly took my plate under the microscope and when I saw the [heartbeat] for the first time I was scared, honestly. I had to look down and look back again,” he told the Guardian before his talk. “It was overwhelming for me. People get emotional when you see the heartbeat.”
The work highlights the astonishing pace of progress and fierce rivalry in the field. Days before Neupane’s work was revealed, Prof Magdalena Zernicka-Goetz unveiled a groundbreaking human embryo model that mirrored features seen at about 14 days, the legal cutoff for cultivating natural embryos in the lab. Within a day, three international competitors had posted their own preprint papers online in response.
The latest embryo model, described by Neupane, replicates some of the most advanced features to date, including beating heart cells, which typically emerge at day 23 in a natural embryo, and traces of red blood, which would appear in the fourth week. The structures were grown in culture from embryonic stem cells and transferred into a rotating bottle, designed to act as a basic artificial uterus. The structures did not have the beginnings of a brain and since they lacked the placenta and yolk sac precursors, which are crucial for guiding development, they began to diverge from natural development path over time.
“At the later time points they don’t have all the features of embryos,” Neupane said. “It would be dangerous to compare them directly to in vivo embryos.”
The findings are yet to be published as either a preprint or a peer-reviewed journal paper.
Prof Robin Lovell-Badge, the head of stem cell biology and developmental genetics at the Francis Crick Institute in London, who was not involved in the work, said synthetic embryos that lack the placenta and yolk sac structures should be treated very differently from so-called integrated embryos “because they could not possibly develop to be implanted to form a child”.
“The heart is just a pump,” he added. “I know we think it quickens in response to our emotions. But it’s the brain that is the seat of our emotions, not our heart.”
International guidelines place this type of embryo model in a similar risk category to brain organoids or lab-grown human heart tissue.
These lab-grown entities could provide crucial insights into a “black box” period of early development to help understand the impact of genetic disorders and the causes of recurrent miscarriage. They could also be used to screen the effect of drugs on embryos and study the link between gestational diabetes and heart defects in babies. Eventually, they could be used for regenerative medicine, to create personalised grafts of heart or liver tissue that could act as a bridge for patients waiting for donor organs.
Sarah Norcross, director of the Progress Educational Trust, a charity that helps people struggling with infertility and genetic conditions, said: “The sophistication of the stem-cell-based embryo models that can now be created is testament to the talent of the researchers working in this area. For all this sophistication, however, we must remember that these models are not actual human embryos.”