Scientists have used embryonic stem cells to create three-dimensional early-stage human embryos that are more complex than any previous lab-generated embryo model. The researchers hope these structures or 'embryoids' will provide crucial insights into the earliest events underlying human development.
During development the embryo must establish a body plan or 'blueprint' so that the embryonic cells receive the correct signals to generate the different organs of the body. As these very early events occur in the womb they are extremely challenging to study, and as a result this period is often referred to as the 'black box of development'.
'We came up with a model of human embryos that is developed outside of the womb and is not the product of the sperm and the eggs but is the product of human embryonic stem cells that self-organise into complicated structures,' said lead scientist, Dr Ali Brivanlou at Rockefeller University in New York City, New York.
He and his colleagues created the embryoids by placing dissociated cells into a dish containing hydrogel and extracellular matrix scaffolding and found that they organised themselves into balls that resembled early embryos. Crucially, the researchers were then able to drive the embryoids through the next stage of development where the balls of cells 'break symmetry' forming a structure with a front and a back.
'This process of symmetry breaking is a major holy grail of development biology,' Dr Brivanlou told NPR. 'I really feel like I'm looking at one of the most mysterious aspects of our own existence.'
The model has been hailed a major development by top scientists in the field. 'Scientifically, this research is important,' said Dr George Daley, a stem-cell scientist and the dean of the Harvard Medical School in Cambridge, Massachusetts, who was not involved in the study. 'We really don't have access to the earliest stages of development. And here we have this remarkable tool in a petri dish.'
The work however has started to raise some questions about how far scientists should go in creating living models of human embryos.
Dr Insoo Hyun, a bioethicist at Case Western Reserve University in Cleveland, Ohio, and Harvard Medical School who was not involved in the research asked: 'As the embryo models become much more complete and much further along in showing us how the human body develops after fertilisation, one might begin to wonder: at what point do these models effectively just become the real thing?'
According to current ethical guidelines that stem cell researchers follow, scientists are prohibited from studying human embryos in the lab beyond 14 days of development.
This research 'certainly hints that science is headed towards a challenge to that rule', added Dr Daley.
But the Rockefeller researchers insisted the embryo structures produced in this study do not have the ability to develop into later embryonic stages. 'These are not actual human embryos,' said Dr Mijo Simunovic, study first author. 'And they would never become human embryos if we let them grow.'
The research was published in Nature Cell Biology.