Administration of tiny cargo-carrying vesicles called exosomes derived from human umbilical cord blood eased motor and cognitive dysfunction in a mouse model of Parkinson’s disease, according to a recent report.
The exosomes were able to prevent neurodegeneration, promote nerve cell regeneration, and protect against dysregulated cellular processes implicated in Parkinson’s.
Scientists believe the exosomes could offer a safe, effective, and easily obtained treatment strategy, but more studies are still needed to optimize the approach for clinical use.
The study, “Umbilical cord blood-derived exosomes attenuate dopaminergic neuron damage of Parkinson’s disease mouse model,” was published in the Journal of Nanobiotechnology.
Parkinson’s disease is caused by the progressive loss of nerve cells that produce a signaling chemical called dopamine in the brain, or dopaminergic neurons.
Stem cells thought to have various therapeutic properties
Stem cells are a group of cells with the unique ability to mature into virtually any other type of cell in the body. They’re thought to have various therapeutic properties, including anti-inflammatory, wound healing, anti-aging, and regenerative effects.
As such, therapeutic delivery of stem cells is of interest for various diseases, including Parkinson’s. However, the approach has some limitations, including that they can cause an immune response in the recipient that limits the therapy’s efficacy and safety.
Exosomes are small vesicles released from cells that carry a variety of molecules, including DNA and proteins, to other nearby cells. They can be collected from a variety of sources, but umbilical cord blood (UCB) is a rich source of them.
Among the cargo in UCB exosomes are stem-cell-derived substances, as well as anti-aging factors. As such, these exosomes could offer the same therapeutic benefits of stem cells, but are more easily collected and have a lower risk of causing immune reactions.
This approach was found to have anti-aging effects in preclinical studies, but it hasn’t yet been evaluated for therapeutic benefits in neurodegenerative diseases that generally affect an aging population.
In their recent study, scientists explored the therapeutic benefits of UCB exosomes in a mouse model of Parkinson’s.
Exosomes were isolated from human UCB and injected into the bloodstream of the mouse model. Results showed the exosomes led to motor recovery in the mice, with stronger effects than other isolated components of UCB. When injected into the bloodstream, the exosomes could cross over into the brain and be taken up by dopaminergic neurons.
More detailed behavioral experiments showed the exosomes, when administered before disease onset, could prevent the development of motor dysfunction and cognitive declines. When treatment was started after those symptoms had already emerged, it was still able to ease motor dysfunction and cognitive decline that had developed.
Exosomes found to protect against loss of dopaminergic neurons
Along with these symptom benefits, the UCB exosomes were found to protect against the loss of dopaminergic neurons, lower levels of alpha-synuclein, which is a protein that toxically accumulates in the Parkinson’s brain, and alleviate neuroinflammation.
The exosomes were associated with an increase in neuron precursor cells that had been diminished in the Parkinson’s model, suggesting the treatment might actually promote nerve cell regeneration.
Experiments in cell cultures revealed the exosomes had the capacity to sustain normal cellular energy metabolism, slow accelerated cellular aging, and prevent oxidative stress, a type of cell damage implicated in the neurodegenerative condition.
Underlying these benefits was the ability of the exosomes to prevent overactivation of a signaling pathway called MAPK p38/ERK.
“The findings hold significant implications for the clinical application of [UCB exosomes] in the treatment of neurodegenerative diseases,” the researchers wrote.
However, before using UCB exosomes in the clinic, their safety will have to be confirmed in humans. Moreover, more research is needed to better understand which components of the exosomes have therapeutic properties.
“It is crucial to identify the target molecules within the exosome and develop drugs or engineered exosomes to regulate these target molecules for clinical trials,” the researchers wrote. “Therefore, it is our future research direction to obtain specific cell-derived exosomes after classifying stem cells from UCB and develop renewable and reliable engineered exosomes for the treatment of Parkinson’s disease.”
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