دورية أكاديمية

Mesenchymal stem cell-derived extracellular vesicles ameliorate Alzheimer's disease-like phenotypes in a preclinical mouse model.

التفاصيل البيبلوغرافية
العنوان: Mesenchymal stem cell-derived extracellular vesicles ameliorate Alzheimer's disease-like phenotypes in a preclinical mouse model.
المؤلفون: Cone AS; Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA., Yuan X; Department of Chemical and Biomedical Engineering, Florida A&M University and Florida State University College of Engineering, Tallahassee, FL 32306, USA.; The National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida 32310, USA., Sun L; Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA., Duke LC; Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA., Vreones MP; Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA., Carrier AN; Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA., Kenyon SM; Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA., Carver SR; Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA., Benthem SD; Department of Neuroscience, Florida State University College of Psychology, Tallahassee, FL 32306, USA., Stimmell AC; Department of Neuroscience, Florida State University College of Psychology, Tallahassee, FL 32306, USA., Moseley SC; The National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida 32310, USA., Hike D; Department of Chemical and Biomedical Engineering, Florida A&M University and Florida State University College of Engineering, Tallahassee, FL 32306, USA.; The National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida 32310, USA., Grant SC; Department of Chemical and Biomedical Engineering, Florida A&M University and Florida State University College of Engineering, Tallahassee, FL 32306, USA.; The National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida 32310, USA., Wilber AA; Department of Neuroscience, Florida State University College of Psychology, Tallahassee, FL 32306, USA., Olcese JM; Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA., Meckes DG Jr; Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA.
المصدر: Theranostics [Theranostics] 2021 Jul 13; Vol. 11 (17), pp. 8129-8142. Date of Electronic Publication: 2021 Jul 13 (Print Publication: 2021).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101552395 Publication Model: eCollection Cited Medium: Internet ISSN: 1838-7640 (Electronic) Linking ISSN: 18387640 NLM ISO Abbreviation: Theranostics Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Wyoming, N.S.W. : Ivyspring International Publisher, 2011-
مواضيع طبية MeSH: Mesenchymal Stem Cell Transplantation*, Alzheimer Disease/*therapy, Amyloid beta-Peptides/metabolism ; Animals ; Brain/metabolism ; Disease Models, Animal ; Extracellular Vesicles/metabolism ; Hippocampus/metabolism ; Immunomodulation ; Mesenchymal Stem Cells/metabolism ; Mice ; Mice, Transgenic ; Plaque, Amyloid/metabolism
مستخلص: Alzheimer's disease (AD) is an irreversible neurodegenerative disorder that affects more than 44 million people worldwide. Despite the high disease burden, there is no effective treatment for people suffering from AD. Mesenchymal stem cells (MSCs) are multipotent stromal cells that have been widely studied due to their therapeutic potential. However, administration of cells has been found to have a multitude of limitations. Recently, extracellular vesicles (EVs) derived from MSCs have been studied as a therapeutic candidate, as they exhibit similar immunoprotective and immunomodulatory abilities as the host human MSCs. Methods: To test the potential therapeutic effects of MSC EVs, human bone-marrow derived MSCs were grown in three-dimensional (3D) cell culture, and small EVs were harvested using differential ultracentrifugation. These small EVs were given to non-transgenic (NT) or 5XFAD (5 familial Alzheimer's disease mutations) mice intranasally (IN) every 4 days for 4 months. The mice were then required to perform a variety of behavioral assays to measure changes in learning and memory. Afterwards, immunohistochemistry was performed on brain slices to measure amyloid beta (Aβ) and glial fibrillary acidic protein (GFAP) levels. Results: The data revealed that 5XFAD mice that received hMSC-EV treatment behaved significantly better in cognitive tests than saline treated 5XFAD mice, with no significant change between EV-treated 5XFAD mice and NT mice. Additionally, we found lower Aβ plaque load in the hippocampus of the EV-treated mice. Finally, less colocalization between GFAP and Aβ plaques was found in the brain of EV-treated mice compared to saline. Conclusions: Taken together, these data suggest that IN administration of MSC-derived EVs can slow down AD pathogenesis.
Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
(© The author(s).)
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معلومات مُعتمدة: R00 AG049090 United States AG NIA NIH HHS; R01 AG070094 United States AG NIA NIH HHS; R01 CA204621 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Alzheimer's disease; exosomes; extracellular vesicles; mesenchymal stem cells; microvesicles
المشرفين على المادة: 0 (Amyloid beta-Peptides)
تواريخ الأحداث: Date Created: 20210810 Date Completed: 20220119 Latest Revision: 20231107
رمز التحديث: 20231107
مُعرف محوري في PubMed: PMC8344012
DOI: 10.7150/thno.62069
PMID: 34373732
قاعدة البيانات: MEDLINE
الوصف
تدمد:1838-7640
DOI:10.7150/thno.62069