A scientist at the University of Latvia claimed a journal’s Young Investigator Award for her research showing how small vesicles derived from stem cells could lessen motor symptoms in a rat model of Parkinson’s disease.
Karīna Narbute’s work establishes a proof of concept for the potential of small vesicles — called extracellular vesicles — as a minimally invasive therapy to delay progression and disability in Parkinson’s patients.
The Young Investigator Award is given by STEM CELLS Translational Medicine to a young researcher who was the first author of a study, published over the course of a year, deemed to be of scientific importance by the journal’s editorial board.
“More than 10 million people worldwide are living with Parkinson’s Disease, and, while there are therapies to help treat the symptoms, this proof-of-concept study shows the therapeutic potential of extracellular vesicles derived from stem cells to potentially delay disease progression,” Anthony Atala, MD, editor-in-chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine, said in a press release.
Extracellular vesicles, or EVs, are non-replicating particles naturally released by all cells in the body. They carry cargo that can include proteins, and DNA and RNA molecules from a donor cell, and have the potential to alter the behavior of distant recipient cells.
Recipient cells include those within the brain, because extracellular vesicles can cross the blood-brain barrier — the highly selective membrane that shields the central nervous system (CNS) from the general blood circulation.
Previous preclinical studies have shown that extracellular vesicles released from stem cells in the bone marrow preserved memory when delivered via intranasal administration to the brains of mice with epileptic episodes.
Intranasal administration of EVs containing a potent antioxidant, called catalase, also showed significant neuroprotective effects in a Parkinson’s animal model.
In their study, Narbute and colleagues investigated extracellular vesicles, delivered via the nose, in a rat model of Parkinson’s.
To mimic the disease, the rats were injected with 6-hydroxydopamine (6-OHDA) to the brain’s nigrostriatal dopaminergic pathway. This neurotoxin kills dopamine-producing neurons, those responsible for releasing the neurotransmitter dopamine, a chemical messenger that allows nerve cells to communicate and helps to regulate movement.
This rat model “has been proven to be the most accurate to display gait changes and dopaminergic system damage specific to PD [Parkinson’s disease],” the team wrote.
Researchers then isolated extracellular vesicles from stem cells located in the dental pulp, the innermost part of a tooth.
Stem cells from the dental pulp of human exfoliated deciduous teeth, called SHEDs, are easily obtained and have been shown to carry unique neurogenic properties. SHEDs are known to be able to mature into dopaminergic neuron-like cells, and into the Schwann cells responsible for producing myelin, the protective coat surrounding nerve cells.
Narbute’s team isolated extracellular vesicles from SHEDs collected from the deciduous teeth tissue of a child. The vesicles were given intranasally to rats seven days after the neurotoxin’s use. Those treated received a total of 43 × 108 EVs over 15 days.
Treatment effectiveness was measured by the CatWalk gait test, a standard test of motor function and coordination in rodent models of neurological disorders.
In this test, the rats cross an illuminated glass platform, while a video camera records from below. The test registers several gait-related parameters, such as stride pattern, individual paw swing speed, stance duration, and stand duration.
Gait impairments in these rats were not evident at seven days after the neurotoxin was administered, but were significant across all gait measures 20 days later, the researchers reported.
Results from the CatWalk test given at day 20 supported intranasal treatment with extracellular vesicles as significantly lessening several gait problems. Specifically, treated rats’ standing duration, stride length, and step cycle were all now indicative of better coordination and posture.
“Animals felt more stable to walk and took a step significantly faster compared with 6-OHDA-lesion group rats,” the researchers wrote. Treated rats were also able to freely cross the walkway.
Treatment with extracellular vesicles also significantly decreased the number of rotations observed in rats after the neurotoxic injection, as assessed by the apomorphine rotation test. This test is used to evaluate a dopaminergic neuron lesion, as the animals tend to circle toward the side with a lesion.
Motor benefits reported also correlated with a return to normal levels of tyrosine hydroxylase — an enzyme involved in the production of dopamine — in the striatum and substantia nigra, two brain regions particularly affected in Parkinson’s that regulate voluntary movement control.
“Our proof of concept study demonstrates that [extracellular vesicles] could be potentially exploited for the development of novel and minimally invasive therapies that delay progression of the disease and mitigate disability in PD patients,” the researchers wrote.
“Even though we have shown that EVs possess therapeutic properties to reverse neurodegeneration, we still have a lot of work ahead of us,” Narbute added in the released, including a way “to determine the exact molecular mechanisms that underlie the beneficial effects of EVs.”
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