That is according to a new study into these biological parcels which are continuously deployed from all cells in the body loaded with contents that other cells may unpack and use.

By sending exomes off, cells communicate with each other via shared proteins and genetic material.

They were once thought to be microscopic sacks of cellular waste, but are now understood to hold immense importance for our health.

Increasing research in recent years has even shown they can transport molecules that are linked to the spread of cancer and neurodegenerative disorders such as Alzheimer’s.

Their role in brain development has remained a mystery until now, however.

New research shows that exosomes are not only integral to the development of neurons and neural circuits, but they can restore health to brain cells affected by developmental disease.

The US-based study, published in Proceedings of the National Academy of Sciences, was led by Hollis Cline and her colleagues at Scripps Research.

Cline says: “During different stages of brain development, signalling between cells is absolutely essential. We found that exosomes are one of the ways cells communicate these signals.”

Spherical containers called vesicles distribute different materials within and among cells. Exosomes are a type of vesicle tasked specifically with transporting various biological cargo -lipids, proteins, RNA – from one cell to another.

Cline’s research shows that proteins in particular, were responsible for the cell-to-cell signalling capabilities of exosomes.

Her research team examined exosomes from healthy human neurons and those from a disease model of Rett syndrome, a genetically-driven developmental brain disorder that causes autism-like symptoms.

Pranav Sharma, a neuroscientist in Cline’s lab, designed experiments to clearly identify and compare exosome bioactivity from healthy neurons and diseased neurons.

Through multiple cellular and functional assays, they found that the Rett-affected exosomes didn’t contain any harmful proteins, but also didn’t have essential signalling proteins found in healthy exosomes. “They did not have bad stuff, but lacked the good stuff,” Sharma says.

As part of the experiment, the team used ‘CRISPR’ gene editing technology to correct the mutation that causes Rett syndrome, and then examined whether the signalling functions of the neural exosomes were restored as a result. “Fixing the mutation reversed the deficits,” Sharma says.

They also tested whether adding healthy exosomes to a culture-dish model of Rett syndrome would provide a therapeutic effect. It did.

“That was perhaps our most exciting finding: that exosomes from healthy cells can indeed rescue neurodevelopmental deficiencies in cells with Rett syndrome,” Cline says.

“We see this as very promising because of the many neurodevelopmental disorders in need of a treatment. These are disorders for which we already have a deep understanding of the underlying gene deficiencies but are still lacking a therapy to address the disease itself.”

Sharma says the study relied on human neurons derived from induced pluripotent stem cells (iPSCs) from Rett patients.

For this aspect of the experiment, the team drew on the expertise of Alysson Muotri, a neuroscience and stem cell specialist at University of California, San Diego.

To characterise the exosomes, the team collaborated with several others from Scripps Research, including mass spectrometry pioneer John Yates III and scientist Daniel McClatchy.

“The brain is a very complicated organ, and neurons are more complex than normal cells,” Sharma says. “We didn’t want to get lost in the complexity, so we decided on a reductionist approach to test what these vesicles are capable of and what they contain.”

They also injected healthy exosomes into a mouse hippocampus – the brain region involved in learning and memory. They observed increased neuron proliferation. This in vivo facet of the study proved that the exosome bioactivity seen in cell cultures carried over to an animal model.

Cline and her team now intend to explore new questions related to exosome bioactivity and potential clinical applications: Could exosomes be measured in a blood test to detect disease or treatment efficacy? Do these findings also apply to autism spectrum disorders (ASDs) and other neurodevelopmental diseases, such as Fragile X? Could exosome-based therapies one day help patients with brain disorders?

“This research has huge relevance for many diseases related to brain development,” Cline says. “It’s very interesting biology that has a lot of scientists excited about the possibilities.”

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