Neurons grown in the lab reach maturity for the first time, opening a new window into studying neurodegenerative disease.
Researchers from Northwestern University, Chicago, have used the 'dancing molecule' technique to create neurons with advanced maturity from human induced pluripotent stem cells (hiPSCs). Neurons have been derived from hiPSCs previously, but were functionally immature.
Professor Samuel Stupp, co-author of the study, explained why immature neurons are not useful in studying neurodegenerative diseases. 'When you have an iPSC that you manage to turn into a neuron, it's going to be a young neuron. But, in order for it to be useful in a therapeutic sense, you need a mature neuron. Otherwise, it is like asking a baby to carry out a function that requires an adult human being.'
Neurons are a type of brain cell that communicate with other neurons in the brain and send messages throughout the nervous system to muscles and tissues. The study, published in Cell Stem Cell, describes hiPSC-derived neurons plated on a synthetic scaffold of nanofibres containing fast-moving 'dancing molecules'.
The dancing molecule technique was previously developed by Professor Stupp in 2021 and published in Science, where he discovered how to control the movement of molecules so they are able to find and communicate with constantly moving receptors.
In his current research he controlled the collective movement of more than 100,000 molecules within the nanofibre scaffold, with the synthetic 'dancing molecules' mimicking the movement of biological molecules and communicating with the hiPSC-derived neurons. Professor Stupp said: 'The reason we think this works is because the receptors move very fast on the cell membrane and the signaling molecules of our scaffolds also move very fast,'.
Not only did the hiPSC-derived neurons have advanced maturation, they also had better signaling and branching capabilities, and were less likely to clump together (a challenge of previous hiPSC-derived neuron models).
As part of the study, the researchers used hiPSC-derived motor neurons from a patient with motor neurone disease. This disease, also known as amyotrophic lateral sclerosis or ALS, leads to the degeneration of neurons in the brain and spinal cord, resulting in progressive paralysis and eventual death. The scientists matured the neurons using the dancing molecules technique and found they exhibited pathology reminiscent of post-mortem ALS tissue.
'For the first time, we have been able to see adult-onset neurological protein aggregation in the stem cell-derived ALS patient motor neurons. This represents a breakthrough for us,' said Dr Evangelos Kiskinis, co-author of the study, 'It's unclear how the aggregation triggers the disease. It's what we are hoping to find out for the first time.'
The authors hope that creating healthy, highly functional neurons will not only aid in the development of novel neurodegenerative disease therapeutics, but may also be used to transplant healthy neurons into a patient with spinal cord injury to replace damaged or lost neurons.
Sources and References
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Mature 'lab grown' neurons hold promise for neurodegenerative disease
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Artificial extracellular matrix scaffolds of mobile molecules enhance maturation of human stem cell-derived neurons
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How 'dancing molecules' can improve the way we study neurodegenerative disease
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Could lab-grown neurons be used to treat Alzheimer's?
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