Protection + anti-inflammatory, intranasal administration of mesenchymal stem cells brings hope for Alzheimer’s

Mesenchymal stem cells and their secreted extracellular vesicles (MSC-EVs), because of their protective and anti-inflammatory properties, bring hope for the effective treatment of Alzheimer’s disease.

When looking for a treatment for Alzheimer’s disease, mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) are promising because of their protective and anti-inflammatory properties. A new mouse study published in the journal STEM CELLS Translational Medicine on June 4th proved for the first time that intranasal injection of MSC-EVs can reduce inflammation, which is considered to be The main factor of Alzheimer’s disease reinforces this view. They also trigger actions that protect brain neurons from further degradation.

The study was published in the journal “Stem Cell Translational Medicine” on June 4
The research, led by Dr. Silvia Coco of the University of Milano-Bicocca in Italy, laid the foundation for future research that may indicate a cure for this devastating disease.
Alzheimer’s disease is an irreversible neurodegenerative disease that can lead to the destruction of memory, cognition, personality and other functions, and ultimately death. According to a 2018 report by the International Alzheimer’s Association, 50 million people worldwide suffer from Alzheimer’s disease or other dementias, and the cost of treatment is estimated to exceed US$1 trillion.
Although it is believed that abnormal amyloid plaques in the brain play an important role in Alzheimer’s disease, there is increasing evidence that inflammation is also the key to its development. This increases the necessity of targeting brain immune cells to slow down disease progression.

University of Milan Bicoca
The beneficial effects of MSC-EVs found in Alzheimer’s disease in regulating inflammation have been reported in several different studies on mice. This is due to the ability of mesenchymal stem cells to regulate the body’s immune system, which in turn is believed to be the result of EVs release. These nano-sized membrane-bound vesicles transport DNA, including DNA, RNA, and proteins, as a form of cell-to-cell communication. They are also thought to remove harmful substances from cells.
In earlier studies, MSC-EVs were injected intravenously or directly into the ventricle of the brain over an extended period of weeks or months. The difference in this latest study is that the administration of MSC-EVs is done through the nasal passages and the administration time is much shorter. Dr. Coco said: “We believe that the possibility of applying MSC-EVs through a non-invasive route and the proof of its anti-inflammatory effects may accelerate the chance of using MSC-EVs to treat Alzheimer’s disease.”

The team conducted research in vitro (outside of living organisms) and in vivo (in vivo). They first collected MSCs from the bone marrow of healthy human donors and pre-treated them with proteins called cytokines to enhance the anti-inflammatory capacity of MSCs and promote their EVs release. In the in vitro phase of their research, they added the generated MSC-EVs to microglia (microglia mediate the immune response of the central nervous system and are therefore the targets of Alzheimer’s disease), microglia The cells were isolated from newborn C57BL/6 mice (these mice were specially bred to study diseases including Alzheimer’s disease). The application interval is 2 to 24 hours. The results were analyzed 48 hours after the final application.
In the in vivo part of the study, the research team injected a group of 7-month-old Alzheimer’s disease female mice with two doses of MSC-EVs through nasal injection. The second injection was only 18 hours after the first injection . After 21 days, when they evaluated the results, they found that, as they saw in in vitro experiments, MSC-EVs inhibited the activation of microglia in the mouse brain and increased dendritic spines (providing cognitive flexibility in the brain) Structure).
Dr. Coco said: “We think the amazing thing about this study is that the observed effect can be achieved by only two intranasal injections of MSC-EVs. This may be because the intranasal delivery of EVs may achieve more than other methods. High level.”

The effect of intranasal injection of pre-treated MSC-secreting EVs (MSC-EVs) on the activation of microglia in the brain of 3xTg-AD mice. The image shows the distribution of Iba-1+-microglia (green) in the hippocampus inside CA1 of PBS-(CTRL) and EV-treated (MSC-EVs) mice. The nuclei (blue) are stained with DAPI. Scale bar: 100mm.
“Our findings reinforce the view that when treating Alzheimer’s disease, in addition to removing amyloid plaques from the brain, other mechanisms of action should be valued,” she added. Doubt, we must consider the possibility of obtaining greater effects through repeated intranasal injections, which will be a direction for future experiments.”
“This research has several important findings. Anthony Atala, MD, chief editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine, said: “In search of treatment As a possible method of Alzheimer’s disease, people are studying mesenchymal stem cells and their secreted extracellular vesicles (MSC-EVs) because of their protective and anti-inflammatory properties. The results of this study provide an opportunity for potentially effective therapies, which can be tested in human clinical trials. This work is worth moving forward. “

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