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Scientists grow a ‘notochord’ for the first time in the lab

Electron scanning microscopy image showing a very detailed look at pieces of trunk organoids. Credit: Tiago Rito, Marie-Charlotte Domart.

Scientists have figured out how to coax human stem cells to develop into the “notochord”, which plays a critical role in organising tissue in developing human embryos and later becomes the intervertebral discs of the spinal column.

The UK team made pluripotent stem cells – which can turn into any cell of the body –  form into the “trunk-like” organoid, which spontaneously elongated to 1-2mm in length.

It contained developing neural tissue and bone stem cells, arranged in a pattern that mirrors development in human embryos.

“The notochord acts like a GPS for the developing embryo, helping to establish the body’s main axis and guiding the formation of the spine and nervous system,” says James Briscoe of the Francis Crick Institute in the UK, senior author of a Nature study describing the work.

“Until now, it’s been difficult to generate this vital tissue in the lab, limiting our ability to study human development and disorders.

“Now that we’ve created a model which works, this opens doors to study developmental conditions which we’ve been in the dark about.”

The notochord is a rod-shaped tissue found in the developing bodies of all chordates, a phylum of the animal kingdom that includes vertebrates (which have a backbone).

But due to the notochord’s complexity, it hasn’t been successfully grown in organoid models of human spine and nervous system (trunk).

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Two worm-like representation of the trunk organoidMicroscopy image of the surface of a trunk organoid (top) and a computer-generated image (bottom) with notochord in green, surrounded by outer neural tissue (skeletonised in purple). Credit: Tiago Rito

“Finding the exact chemical signals to produce notochord was like finding the right recipe,” says first author of the study, Tiago Rito.

“Previous attempts to grow the notochord in the lab may have failed because we didn’t understand the required timing to add the ingredients.

“What’s particularly exciting is that the notochord in our lab-grown structures appears to function similarly to how it would in a developing embryo.

“It sends out chemical signals that help organise surrounding tissue, just as it would during typical development.”

The researchers believe the new findings pave the way for future studies of birth defects affecting the spine and spinal cord.

It could also provide insight into conditions affecting the intervertebral discs, which develop from the notochord. These discs sit between the vertebrae and act like shock absorbers for the spine.

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