A study led by MND Association funded researcher Prof Siddharthan Chandran from the University of Edinburgh has developed a new method to create a diverse group of motor neurones from stem cells. The research, published in the journal Nature Communications could be used to create more accurate and clinically relevant laboratory dish models to learn more about the differences in vulnerability and connectivity of motor neurones in MND.
Why are the subtypes of motor neurones important to MND research?
When we first start to develop as embryos in the womb, chemical messages are used as cues to tell our cells what to turn in to. At the start of this process our cells can be thought of as blank canvases that have the potential to turn into any type of cell. Mixtures of ‘colourful’ chemicals are then used to create a unique ‘hue’ signal in order for the cell to know what to become.
So, depending on the ‘hue’ of chemicals around them, neuronal precursor cells will turn into different subtypes of motor neurone. In their fully formed state, these motor neurones subtly vary in their chemical makeup (due to acting on the different ‘hue’ signals given), their vulnerability to degenerate in MND, as well as the way they connect and communicate with other cells.
The subtle differences in subtypes of motor neurone have not been replicated in a laboratory dish model of MND to date. However, being able to develop such a model would provide MND researchers with a true spectrum of the way that MND affects the different subtypes of motor neurones. They would then also be able to develop new and better treatments that can target specific types of motor neurones that may be more vulnerable to MND.
What did the researchers do to find this?
The collaborative research group from Universities of Edinburgh, Cardiff and Cambridge tested a new method for creating different types of motor neurones in a dish from human embryonic stem cells.
To do this, they first added a chemical that accelerates the process of turning stem cells into neurone precursor cells – it’s the equivalent of being able to add a ‘quick drying’ additive to a painting. By adding this chemical, which has been given the catchy name of SB431542, the process of changing an embryonic stem cell into motor neurone progenitor cells is sped up from approximately 30 days to just 12 days.
They then tested whether a certain chemical called ‘retinoic acid’ is needed for the process of making different types of motor neurone. By measuring the chemical makeup of the functional motor neurones produced without retinoic acid, they were able to determine that they had produced a different type of motor neurone that is different from those created with the use of retinoic acid.
By defining a new process to create new and better models using stem cell technology, a new multi-motor neurone type model could be created for MND to study the similarities and differences between motor neurones in MND.
By learning more about these differences, we could learn more about how and why some motor neurones remain spared in MND.