Researchers have made significant advancements in understanding neuromuscular diseases by developing a two-dimensional neuromuscular junction model using pluripotent stem cells. This model, enabling high-throughput drug screening, complements their previously developed three-dimensional organoids. (Artist’s concept.) Credit: SciTechDaily.com
Scientists have developed a groundbreaking two-dimensional model to study neuromuscular diseases, enabling efficient drug testing and enhanced understanding of diseases like spinal muscular atrophy and amyotrophic lateral sclerosis.
Researchers have so far identified around 800 different neuromuscular diseases. These conditions are caused by problems in the way muscle cells, motor neurons, and peripheral cells interact. These disorders, including amyotrophic lateral sclerosis and spinal muscular atrophy, lead to muscle weakness, paralysis, and in some cases death.
“These diseases are highly complex, and the causes of the dysfunction can vary widely,” says Dr. Mina Gouti, head of the Stem Cell Modeling of Development and Disease Lab at the Max Delbrück Center. The problem might lie with the neurons, the muscle cells or the connections between the two. “To better understand the causes and find effective therapies, we need human-specific cell culture models where we can study how motor neurons in the spinal cord interact with the muscle cells.”
Innovative Research Using Organoids
The researchers working with Gouti had already developed a three-dimensional neuromuscular organoid (NMO) system. “One of our goals is to use our cultures for large-scale drug testing,” says Gouti. “The three-dimensional organoids are very large and can’t be grown for a long time in the 96 well culture dish that we use to perform high-throughput drug screening studies.”
![2D Neuromuscular Junction Model](https://scitechdaily.com/images/2D-Neuromuscular-Junction-Model-777x437.jpg)
A human self-organizing 2D neuromuscular junction model. Immunofluorescence analysis of the whole dish shows muscle cells (magenta) organized in bundles surrounded by spinal cord neurons (cyan). Credit: Alessia Urzi, Max Delbrück Center
For this type of screening, an international team led by Gouti has now developed a self-organizing neuromuscular junction model using pluripotent stem cells. The model contains neurons, muscle cells, and the chemical
” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>synapse named neuromuscular junction that is needed for the two types of cells to interact. The researchers have now published their findings in the journal DOI: 10.1038/s41467-023-43781-3