Will your competent? doctor and hospital get further protocol creation going because of your risk of Parkinsons and dementia? Oh no, you have stroke medical 'professionals' that DO NOTHING! RUN AWAY!
The reason you need dementia and Parkinsons prevention:
1. A documented 33% dementia chance post-stroke from an Australian study? May 2012.
2. Then this study came out and seems to have a range from 17-66%. December 2013.
3. A 20% chance in this research. July 2013.
Parkinson’s Disease May Have Link to Stroke March 2017
Mesenchymal Stem Cell-Derived Extracellular Vesicles: Emerging Therapies for Neurodegenerative Diseases
Authors Chen P, Wang F, Ling B, Zhu Y, Lin H, Huang J, Wang X
Received 24 March 2025
Accepted for publication 26 June 2025
Published 2 July 2025 Volume 2025:20 Pages 8547—8565
DOI https://doi.org/10.2147/IJN.S526945
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Professor Eng San Thian
Puwen Chen,1,2,* Fangsheng Wang,2,* Baodian Ling,2 Yifan Zhu,1,2 Haihong Lin,1,2 Junyun Huang,1 Xiaoling Wang1
1The First School of Clinical Medicine, Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 2Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiaoling Wang, The First School of Clinical Medicine, Gannan Medical University, Ganzhou, People’s Republic of China, Email wangxiaoling1@gmu.cn Junyun Huang, The First School of Clinical Medicine, Gannan Medical University, Ganzhou, People’s Republic of China, Email 13879789666@163.com
Abstract: Neurodegenerative diseases are a group of chronic diseases characterized by a gradual loss of neurons that worsens over time and dysfunction. These diseases are extremely harmful, not only affecting the physical health of the patients, but also having a serious impact on their quality of life. They mainly include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), etc. Their pathogenesis is complex, and it is difficult for the existing treatments to effectively slow down the progression of the disease. In recent years, Mesenchymal Stem Cells (MSCs) have received widespread attention for their anti-inflammatory, immunomodulatory and neuroprotective properties. In this context, MSC-derived Extracellular Vesicles (MSC-EVs) have demonstrated unique therapeutic potential as a cell-free therapeutic strategy. MSC-EVs are rich in bioactive substances such as proteins, lipids, mRNAs and miRNAs, which can pass through the blood-brain barrier and be targeted to the diseased area to regulate neuronal survival, synaptic plasticity and neuroinflammatory responses. In addition, compared with stem cell therapy, MSC-EVs have the advantages of low immunogenicity, easy storage and transportation, and avoiding ethical controversies. However, their clinical application still faces challenges: standardized isolation and purification techniques have not been unified, vesicle loading efficiency and targeting need to be further optimized, and long-term safety needs to be systematically evaluated. This review focuses on the role of MSC-EVs in the development of neurological diseases and explores their possible dual roles, both favorable and unfavorable, in the context of neurological diseases. In addition, this review provides a review of current studies on EVs as potential biomarkers for the diagnosis and treatment of neurodegenerative diseases and provides a comprehensive review of the prospects and challenges of MSC-EVs in clinical applications.
Keywords: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, mesenchymal stem cell, extracellular vesicles
Introduction
Neurodegenerative diseases (NDs) are a group of complex diseases characterized by progressive neuronal degeneration and loss of function, which are usually closely related to ageing. They mainly include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), etc. Alzheimer’s disease primarily impacts memory and cognitive function. It is characterized by the accumulation of amyloid plaques and tau tangles in the brain, leading to progressive neuronal loss. This degeneration results in a spectrum of symptoms ranging from mild forgetfulness to severe dementia.1 Parkinson’s disease is characterized by the degeneration of neurons that produce dopamine in the substantia nigra. The symptoms include tremors, muscle rigidity, bradykinesia, and balance difficulties, often accompanied by non-motor issues such as depression and sleep disturbances.2 Huntington’s disease is a hereditary neurodegenerative disorder caused by abnormal CAG repeat sequences in the HTT gene, resulting in the production of toxic Huntington protein. It is manifested as involuntary dance movements, cognitive decline and mental symptoms, gradually damaging daily life.3 Amyotrophic lateral sclerosis (ALS) is characterized by attacking motor neurons, resulting in muscle weakness, atrophy and paralysis. It affects the motor neurons in the upper and lower limbs, leading to symptoms ranging from limb stiffness and slurred speech to respiratory failure. As there is currently no cure, patients usually survive for 3 to 5 years after diagnosis.4 With the aging of the global population, their incidence is increasing year by year, and they have become an important public health problem that threatens the health of human beings. The pathogenesis of these diseases is complex and varied, involving the interaction of multiple factors such as protein misfolding and abnormal aggregation, mitochondrial dysfunction, oxidative stress, neuroinflammatory response, and epigenetic regulatory abnormalities. The main manifestations are cognitive decline, motor dysfunction, behavioral abnormalities or autonomic dysregulation, which ultimately lead to the loss of self-care ability. Currently, clinical treatment is based on symptomatic support, but cannot effectively slow down or reverse the disease process. In recent years, with the development of molecular biology and regenerative medicine, novel therapeutic strategies targeting pathological protein clearance, neuroprotection and stem cell therapy have attracted much attention, providing a potential direction for breaking through the bottleneck of traditional treatment.5
Mesenchymal Stem Cells (MSCs) are pluripotent stem cells capable of self-renewal and multidirectional development. In recent years, MSC therapy has demonstrated significant potential across various domains, with numerous clinical studies conducted globally, addressing a diverse array of conditions, including but not limited to osteoarthritis, diabetes, cardiovascular diseases, neurological disorders, hepatic diseases, and pulmonary diseases.6 Numerous clinical studies have demonstrated that MSCs possess multidirectional differentiation potential and immunomodulatory effects, originating from diverse sources and exhibiting a degree of safety and efficacy, thereby offering new hope for the treatment of certain intractable diseases.7 Moreover, there are deficiencies including inconsistent therapeutic efficacy, an incompletely understood mechanism, challenges in quality control, and elevated costs. Nonetheless, MSC therapy, as an emerging treatment modality, retains significant potential for widespread application. Currently, MSC therapy remains in the clinical research phase, necessitating further comprehensive investigation into its therapeutic mechanisms, optimization of treatment protocols, enhancement of efficacy and safety, and simultaneous reduction of costs to facilitate its broad clinical application.8
According the MISEV2023 standards, extracellular vesicles (EVs) are lipid bilayer-encased particles released from cells that lack self-replication capabilities (ie, they do not possess a functional nucleus) and play significant roles in intercellular communication, disease diagnostics, and therapeutic applications. EVs comprise small extracellular vesicles (sEVs), microvesicles (MVs), and apoptotic bodies.9 sEVs are extracellular vesicles that are secreted from the interior of the cell via multivesicular bodies (MVBs). They range from 30 to 150 nm in diameter and are extruded from the cell through the fusion of intracellular multivesicular structures with the cell membrane. sEVs are abundant in physiologically active compounds, including proteins, nucleic acids (eg, microRNAs, messenger RNAs, long non-coding RNAs), and lipids.10 MVs denote EVs that are expelled from the cell membrane. sEVs range from 100 to 1000 nanometers in diameter and are generated straight from the cell membrane. Microvesicles encompass an array of bioactive substances, including proteins, nucleic acids, and lipids. Apoptotic bodies are membrane entities, ranging from 500 to 2000 nm in diameter, that are vesicles generated during apoptosis. Apoptotic bodies comprise cellular detritus, nucleic acids, and proteins.9,11 Extracellular vesicles have been linked in studies to the onset and progression of neurodegenerative disorders like Parkinson’s and Alzheimer’s. It might emerge as a novel therapeutic target for neurodegenerative illnesses.12
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