Mesenchymal Stromal Cells-Derived Exosome and the Roles in the Treatment of Traumatic Brain Injury

Mot, Yee Yik; Moses, Emmanuel Jairaj; Yusoff, Narazah Mohd; Ling, King-Hwa; Yong, Yoke Keong; Tan, Jun Jie

doi:10.1007/s10571-022-01201-y

Cited by 10 publications

(13 citation statements)

References 181 publications

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“…Initial stimulation of the Akt pathway starts by activation and phosphorylation of phosphatidylinositol 3-kinase at the plasma membrane, suggesting that the cargo of exosomes and microvesicles contains factors that are carried to the cell surface (40). Secondary messenger phosphatidylinositol (3,4,5)-triphosphate (PIP3) then recruits Akt to the membrane so that it can be fully activated (41). Other studies have corroborated that Akt signaling leads to hyaluronan production.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Mesenchymal stem cells have been shown have anti-inflammatory properties (2) and much of these effects are through secreted soluble components (3). Extracellular vesicles may be an important mediator this beneficial effect (4). Recent studies have isolated extracellular vesicles from mesenchymal stem cells, demonstrating that exosomes and microvesicles alone have regenerative and anti-inflammatory properties (5–7).…”

Section: Introductionmentioning

confidence: 99%

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Exosomes and Microvesicles From Adipose-Derived Mesenchymal Stem Cells Protects the Endothelial Glycocalyx From LPS Injury

Taghavi

Abdullah

Shaheen

et al. 2023

Shock

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Introduction: Endothelial glycocalyx damage occurs in numerous pathological conditions and results in endotheliopathy. Extracellular vesicles, including exosomes and microvesicles, isolated from adipose-derived mesenchymal stem cells (ASCs) have therapeutic potential in multiple disease states; however, their role in preventing glycocalyx shedding has not been defined. We hypothesized that ASC-derived exosomes and microvesicles would protect the endothelial glycocalyx from damage by LPS injury in cultured endothelial cells. Methods: Exosomes and microvesicles were collected from ASC conditioned media by centrifugation (10,000g for microvesicles, 100,000g for exosomes). Human umbilical vein endothelial cells (HUVECs) were exposed to 1 μg/mL lipopolysaccharide (LPS). LPS-injured cells (n = 578) were compared with HUVECS with concomitant LPS injury plus 1.0 μg/mL of exosomes (n = 540) or microvesicles (n = 510) for 24 hours. These two cohorts were compared with control HUVECs that received phosphate-buffered saline only (n = 786) and HUVECs exposed to exosomes (n = 505) or microvesicles (n = 500) alone. Cells were fixed and stained with FITC-labeled wheat germ agglutinin to quantify EGX. Real-time quantitative reverse-transcription polymerase chain reaction was used on HUVECs cell lystate to quantify hyaluron synthase-1 (HAS1) expression. Results: Exosomes alone decreased endothelial glycocalyx staining intensity when compared with control (4.94 vs. 6.41 AU, P < 0.001), while microvesicles did not cause a change glycocalyx staining intensity (6.39 vs. 6.41, P = 0.99). LPS injury resulted in decreased glycocalyx intensity as compared with control (5.60 vs. 6.41, P < 0.001). Exosomes (6.85 vs. 5.60, P < 0.001) and microvesicles (6.35 vs. 5.60, P < 0.001) preserved endothelial glycocalyx staining intensity after LPS injury. HAS1 levels were found to be higher in the exosome (1.14 vs. 3.67 RE, P = 0.02) and microvesicle groups (1.14 vs. 3.59 RE, P = 0.02) when compared with LPS injury. Hyaluron synthase-2 and synthase-3 expressions were not different in the various experimental groups. Conclusions: Exosomes alone can damage the endothelial glycocalyx. However, in the presence of LPS injury, both exosomes and microvesicles protect the glycocalyx layer. This effect seems to be mediated by HAS1.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exosomes and Microvesicles From Adipose-Derived Mesenchymal Stem Cells Protects the Endothelial Glycocalyx From LPS Injury

Taghavi

Abdullah

Shaheen

et al. 2023

Shock

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“…178 Despite the lack of comprehension of the exact mechanisms that cause these effects, evidence has indicated that their anti-inflammatory, angiogenic, neuroprotective, and neurogenic properties may be the primary contributors that account for the observed results in both in vitro and in vivo studies. 179 Bone MSCs-derived exosomes are identified to have neuroprotective properties, stimulate angioneurogenesis, and assist with post-ischemic neurological injury recovery in a mouse stroke experiment. [180][181][182] Studies conducted on bone MSC exosomes uncovered the presence of miR-132-3p and miR-133b, which may mitigate the effects of ROS production, apoptosis, and tight junction disruption in cells exposed to hypoxia/reoxygenation injury.…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

The emerging role of exosomes in communication between the periphery and the central nervous system

Han,

Zhang,

Feng

et al. 2023

MedComm

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Exosomes, membrane‐enclosed vesicles, are secreted by all types of cells. Exosomes can transport various molecules, including proteins, lipids, functional mRNAs, and microRNAs, and can be circulated to various recipient cells, leading to the production of local paracrine or distal systemic effects. Numerous studies have proved that exosomes can pass through the blood—brain barrier, thus, enabling the transfer of peripheral substances into the central nervous system (CNS). Consequently, exosomes may be a vital factor in the exchange of information between the periphery and CNS. This review will discuss the structure, biogenesis, and functional characterization of exosomes and summarize the role of peripheral exosomes deriving from tissues like the lung, gut, skeletal muscle, and various stem cell types in communicating with the CNS and influencing the brain's function. Then, we further discuss the potential therapeutic effects of exosomes in brain diseases and the clinical opportunities and challenges. Gaining a clearer insight into the communication between the CNS and the external areas of the body will help us to ascertain the role of the peripheral elements in the maintenance of brain health and illness and will facilitate the design of minimally invasive techniques for diagnosing and treating brain diseases.

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“…In recent years, a large number of studies have shown that EVs can effectively treat various neurodegenerative diseases, including TBI ( Guedes et al, 2020 ; Mot et al, 2022 ). There have also been conventional meta-analysis showing that EVs can improve neurological dysfunction after TBI ( Muhammad et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of extracellular vesicles of different cell origins in traumatic brain injury: A systematic review and network meta-analysis

et al. 2023

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BackgroundThere was still no effective treatment for traumatic brain injury (TBI). Recently, many preclinical studies had shown promising efficacy of extracellular vesicles (EVs) from various cell sources. Our aim was to compare which cell-derived EVs were most effective in treating TBI through a network meta-analysis.MethodsWe searched four databases and screened various cell-derived EVs for use in preclinical studies of TBI treatment. A systematic review and network meta-analysis were conducted for two outcome indicators, modified Neurological Severity Score (mNSS) and Morris Water Maze (MWM), and they were ranked by the surface under the cumulative ranking curves (SUCRA). Bias risk assessment was performed with SYRCLE. R software (version 4.1.3, Boston, MA, USA) was used for data analysis.ResultsA total of 20 studies were included in this study, involving 383 animals. Astrocyte-derived extracellular vesicles (AEVs) ranked first in response to mNSS at day 1 (SUCRA: 0.26%), day 3 (SUCRA: 16.32%), and day 7 (SUCRA: 9.64%) post-TBI. Extracellular vesicles derived from mesenchymal stem cells (MSCEVs) were most effective in mNSS assessment on day 14 (SUCRA: 21.94%) and day 28 (SUCRA: 6.26%), as well as MWM’s escape latency (SUCRA: 6.16%) and time spent in the target quadrant (SUCRA: 86.52%). The result of mNSS analysis on day 21 showed that neural stem cell-derived extracellular vesicles (NSCEVs) had the best curative effect (SUCRA: 6.76%).ConclusionAEVs may be the best choice to improve early mNSS recovery after TBI. The efficacy of MSCEVs may be the best in the late mNSS and MWM after TBI.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023377350.

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Mesenchymal Stromal Cells-Derived Exosome and the Roles in the Treatment of Traumatic Brain Injury

Cited by 10 publications

References 181 publications

Exosomes and Microvesicles From Adipose-Derived Mesenchymal Stem Cells Protects the Endothelial Glycocalyx From LPS Injury

Exosomes and Microvesicles From Adipose-Derived Mesenchymal Stem Cells Protects the Endothelial Glycocalyx From LPS Injury

The emerging role of exosomes in communication between the periphery and the central nervous system

Efficacy of extracellular vesicles of different cell origins in traumatic brain injury: A systematic review and network meta-analysis

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