Convenient delivery
Mesenchymal stem cells and their extracellular vesicles (MSC-EV) have become a promising direction in the development of Alzheimer's disease treatment due to their protective and anti-inflammatory properties. The results of a new study conducted on mice confirm them, showing for the first time that MSC-EV delivered through the nasal passages reduces inflammation, which is a pathogenetic factor of Alzheimer's disease, and triggers a cascade of biochemical reactions that protects brain neurons from further degeneration.
The study, led by Silvia Coco from the University of Milan Bicocca in Italy, provides the basis for future research that may find a cure for this serious disease.
There is evidence that excessive accumulation of amyloid plaques in the brain plays a major role in the development of Alzheimer's disease. However, more and more evidence suggests that inflammation is also the cause of disease progression. The researchers decided to target the immune cells of the brain to reduce the inflammatory response.
The beneficial effects of MSC-EVs in relieving inflammation observed in Alzheimer's disease have already been described in various studies on mice. MSC-EV are able to modulate the body's immune system by releasing extracellular vesicles. These nanoscale bubbles transport various loads, including DNA, RNA and proteins, carrying out intercellular communication. It is also believed that they rid the cell of harmful substances and waste.
In earlier studies, MSC-EV was injected intravenously or directly into the cerebrospinal fluid circulating in the ventricles of the brain for several weeks or months.
A new study has shown the possibility of introducing MSC-EV through the nasal passages, and the treatment lasted a much shorter time. The possibility of introducing MSC-EV noninvasively and demonstrating their anti-inflammatory effect may increase the likelihood of using MSC-EV for the treatment of Alzheimer's disease.
The group conducted their research in vitro and in vivo. First, they collected MSC from the bone marrow of healthy donors and enhanced them with cytokines to impart anti-inflammatory abilities and accelerate the release of extracellular vesicles. For in vitro research, the obtained MSC-EVs were added to microglia – immune cells of the central nervous system that are targets in the treatment of Alzheimer's disease. Microglia was taken from newborn mice C57BL/6, which are specially bred to study Alzheimer's disease. Applications were made at intervals of two and 24 hours. The results were then analyzed 48 hours after the last procedure.
For the in vivo study, the group administered two doses of MSC-EV to 7-month-old mice with Alzheimer's disease. Applications were performed through the nasal passages, the second dose was given 18 hours after the first. The results were evaluated after 21 days.
As in in vitro experiments, MSC-EV weakened the activation of microglial cells in the brain of mice and increased the density of dendritic spines providing cognitive stability.
Distribution of microglial cells in the brains of mice with Alzheimer's disease without treatment (left) and after intranasal administration of MSC-EV (right). Source: ALPHAMED PRESS.
The main result of the study is that the observed effects were achieved by only two intranasal injections of MSC-EV, performed at intervals of several hours. This proves that extracellular vesicles injected into the nasal passages can reach higher levels in the brain than when delivered by other methods.
Article by M.Losurdo et al. Intranasal delivery of mesenchymal stem cell derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer's disease is published in the journal STEM CELLS Translational Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on EurekAlert: Intranasal delivery of MSCs provides hope for treating Alzheimer's disease.