Human stem cells used to mimic early embryo development

Using human stem cells, scientists from the University of Cambridge have developed a model for early embryo development.

With the 'embryo-like' model, which mimics features of human embryos, the scientists hope to shed light on a crucial developmental process called gastrulation, which lays out the first rudimentary body plan in the embryo. The 14-day limit on cultivating embryos in laboratories, has meant that until now researchers have not been able to observe human gastrulation, which happens after this point.

'This is a hugely exciting new model system, which will allow us to reveal and probe the processes of early human embryonic development in the lab for the first time,' said, first author of the study, Dr Naomi Moris. 'Our system is a first step towards modelling the emergence of the human body plan, and could prove useful for studying what happens when things go wrong, such as in birth defects.'

In collaboration with the Hubrecht Institute in the Netherlands, the scientists in Cambridge have found a way to generate so-called gastruloids. Using mouse embryonic cells, they found that treating a compact colony of stem cells with chemicals can cause them to form 3D structures, which then spontaneously mimic the gastrulation process. The new study, published in Nature, replicated these findings using human stem cells and reported key features of 21-day-old embryos in gastruloids after just 72 hours of cultivation. However, though the gastruloids displayed rudimentary components of a heart and nervous system, they lacked brain features and tissues necessary for implantation in the womb, and thus cannot develop into viable fetuses. 

'It's clear these gastruloids are not embryos and won't develop into embryos,' Dr Jeantine Lunshof, who was not involved in the study, commented, 'but by mimicking embryo features, such models could resolve a lot of problems.'

While gastrulation is seen as a crucial step of human development, the process has never been studied in a laboratory setting. For ethical reasons, many countries limit researchers from growing embryos in the laboratory for longer than 14 days after conception, while gastrulation typically occurs in the third week of embryo development. In the process the embryo's composition drastically changes from a homogeneous cell mass to a structured body plan with a head-to-tail axis. During the formation of this axis, the embryonic stem cells undergo differentiation dictated by location, which leads to the formation of three distinct layers of cells, which later can give rise to all major body systems (ectoderm, mesoderm, endoderm). 

Scientists agree that understanding this key process could reveal new insights into human birth defects and diseases, and potentially help to develop tests for these before birth. 

Nevertheless, Professor Robin Lovell-Badge from the Francis Crick Institute, London, highlighted that the gastruloids will only be validated as model system through direct comparisons of their molecular signatures with those of human embryos. 'This cannot be done in the UK and many other countries for legal reasons, as this would cross the 14-day limit. If the law were changed, however, even a few such cultured embryos might suffice to validate the model. Until then, there will always be doubt about this or other models of human development during this critical, but hidden period.'