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Most sophisticated in vitro mouse embryo created from stem cells

5 July 2021
Appeared in BioNews 1102

A mouse embryo has been developed artificially in a lab from embryonic stem cells that represents the most sophisticated in vitro mammalian model ever created.

Using embryonic stem cells collected from mice, scientists from the University of Virginia have been able to produce a mouse embryo with a beating heart. Muscles, blood vessels, the digestive tract and the nervous system, with the formation of a neural tube, also starting to develop. They achieved this by discovering a way to instruct a group of cells to begin embryonic development. In response to this instruction the cells have developed into embryo-like structures in a process that mirrors embryo growth.

Professor Christine Thisse, who created the model alongside Professor Bernard Thisse, explained: 'We found a way to instruct aggregates of stem cells to initiate embryonic development. In response to this controlled instruction, the aggregates develop into embryo-like entities in a process that recapitulate the embryonic steps one-by-one.' Professor Bernard Thisse added: 'The only way to have all the variety of cells necessary to the formation of functional organs is to develop systems in which all precursor cells are present. The embryo-like entities we have engineered using stem cells are providing just this.'

It is the first in vitro model of a mammalian embryo with so many tissues to be built from stem cells, the researchers claim. Most importantly, those tissues are organised as they should be, around the notochord – the precursor of the vertebral column (spine) – a defining trait of vertebrate animals.

There has been a significant effort in recent years to replicate mammalian embryonic development in the lab. So far, scientists have only been able to produce multicellular structures which mimic parts of organs, known as organoids, from stem cells.

While these organoids are able to mimic the microanatomy of organs, they lack the organisation and full variety of cell types of genuine organs. To obtain this higher level of organisation the organ requires blood vessels and nerves, and needs to contain the full spectrum of cells and tissues.

'Having all the variety of tissues made allows us to hope that the scientific community will be able to build organs with a proper vascularisation, innervation and interactions with other tissues,' said Professor Christine Thisse. 'This is essential to be able one day to produce functional human replacement organs in a dish. This would overcome the shortage of organs for transplants.'

However, this new model is unable to develop into a complete mouse. 'The embryoids we are currently producing lack the anterior brain domains,' Professor Bernard Thisse explained. The development stops at a time corresponding to the middle period of gestation of a mouse embryo. He continued: '... with the techniques we have developed, we should be able, at some point, to manipulate molecular signals that control embryo formation, and this should lead to generating embryo-like entities containing all tissues and organs including the anterior brain.'

The researchers hope that their breakthrough will assist researchers to further understand mammalian development.

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