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Cell-Free Extracellular Vesicles Derived from Human Bone Marrow Endothelial Progenitor Cells as Potential Therapeutics for Microvascular Endothelium Restoration in ALS
- Source :
- Neuromolecular Med
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Repairing the damaged blood-CNS-barrier in amyotrophic lateral sclerosis (ALS) is necessary to prevent entry of detrimental blood-borne factors contributing to motor neuron dysfunction. Recently, we showed benefits of human bone marrow endothelial progenitor cell (hBM-EPC) transplantation into symptomatic ALS mice on barrier restoration by replacing damaged endothelial cells (ECs). Additionally, transplanted cells may endogenously repair ECs by secreting angiogenic factors as our subsequent in vitro study demonstrated. Based on these study results, hBM-EPCs may secrete extracellular vesicles, which may contain and transfer diverse vesicular biomolecules towards maintenance of EC functionality. The study aimed to characterize extracellular vesicles (EVs) derived from hBM-EPCs as potential cell-free therapeutics for endothelium repair in ALS. EVs were isolated from hBM-EPC media at different culture times and vesicle properties were evaluated. The protective effects of EVs on mouse brain endothelial cells (mBECs) exposed to ALS mouse plasma were investigated. Uptake and blockage of EVs from GFP-transfected hBM-EPCs in ECs were determined in vitro. Results showed that EVs isolated from hBM-EPCs as nanosized vesicles significantly reduced mBEC damage from the pathological environment and these EVs were taken up by cells. Blockage of β1 integrin on EVs prevented internalization of vesicles in mBECs. Together, these results provide evidence for potential of hBM-EPC-derived EVs as novel cell-free therapeutics for repair of endothelium in ALS. Although determining translational potential of hBM-EPC-derived EVs will require evaluation in vivo, this in vitro study represents a step towards an extracellular vesicle-based approach for repair of the damaged microvascular endothelium in ALS.
- Subjects :
- Male
0301 basic medicine
Endothelium
media_common.quotation_subject
Bone Marrow Cells
Endothelial progenitor cell
Article
Extracellular Vesicles
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
Superoxide Dismutase-1
0302 clinical medicine
Genes, Reporter
In vivo
medicine
Animals
Humans
Secretion
Progenitor cell
Internalization
Cells, Cultured
Endothelial Progenitor Cells
media_common
Chemistry
Amyotrophic Lateral Sclerosis
Extracellular vesicle
Cell biology
Transplantation
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Neurology
Blood-Brain Barrier
Culture Media, Conditioned
cardiovascular system
Molecular Medicine
Endothelium, Vascular
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15591174 and 15351084
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- NeuroMolecular Medicine
- Accession number :
- edsair.doi.dedup.....2c50ef17721d16b6c6e2c65879b3cac5