Stem Cell-derived Exosomal MicroRNA as Therapy for Vascular Age-related Diseases

Ren, Hang; Guo, Ziyuan; Liu, Yang; Song, Chunli

doi:10.14336/ad.2021.1110

Cited by 8 publications

(8 citation statements)

References 100 publications

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“…SCEVs, including those from mesenchymal stromal cells (MSCEVs), are recognized for their rich miRNA composition, which varies depending on the cell type and microenvironment. The active accumulation of miRNA cargo within vesicles can influence recipient cells suggesting dedicated biological roles of these EVs [ 117 , 118 ].…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

Stem Cell-Derived Extracellular Vesicles in the Treatment of Cardiovascular Diseases

McDonald,

Mohak,

Fabian

2024

Pharmaceutics

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Cardiovascular disease constitutes a noteworthy public health challenge characterized by a pronounced incidence, frequency, and mortality rate, particularly impacting specific demographic groups, and imposing a substantial burden on the healthcare infrastructure. Certain risk factors, such as age, gender, and smoking, contribute to the prevalence of fatal cardiovascular disease, highlighting the need for targeted interventions. Current challenges in clinical practice involve medication complexities, the lack of a systematic decision-making approach, and prevalent drug therapy problems. Stem cell-derived extracellular vesicles stand as versatile entities with a unique molecular fingerprint, holding significant therapeutic potential across a spectrum of applications, particularly in the realm of cardio-protection. Their lipid, protein, and nucleic acid compositions, coupled with their multifaceted functions, underscore their role as promising mediators in regenerative medicine and pave the way for further exploration of their intricate contributions to cellular physiology and pathology. Here, we overview our current understanding of the possible role of stem cell-derived extracellular vesicles in the clinical management of human cardiovascular pathologies.

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Section: Extracellular Vesiclesmentioning

confidence: 99%

Stem Cell-Derived Extracellular Vesicles in the Treatment of Cardiovascular Diseases

McDonald,

Mohak,

Fabian

2024

Pharmaceutics

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“…MicroRNA, a predominant component in hBMSC-sEV, is a type of noncoding RNA with a short, singlestranded that target mRNA sequences by binding the 3′-untranslated regions (3′-UTR), which causes degradation or translation blockade of mRNA [14][15][16][17][18]. Previous studies have shown that the miRNA could regulate and affect a variety of cell function, such as proliferation, invasion, inflammation responses and apoptosis [19][20][21]. A series of miRNAs have been revealed their association with osteogenesis, which participated in the process of bone remodeling, and presented a critical role in the progression of tendon homeostasis and osteoarthritis [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Bone marrow mesenchymal stem cell-derived exosomal microRNA-382 promotes osteogenesis in osteoblast via regulation of SLIT2

Su¹,

Yang²,

Lv³

et al. 2023

J Orthop Surg Res

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Background Osteoporosis (OP) is a systemic skeletal disorder with increased bone fragility. Human bone marrow mesenchymal stem cells (hBMSCs) have multi-lineage differentiation ability, which may play important roles in osteoporosis. In this study, we aim to investigate the role of hBMSC-derived miR-382 in osteogenic differentiation. Methods The miRNA and mRNA expressions in peripheral blood monocytes between persons with high or low bone mineral density (BMD) were compared. Then we collected the hBMSC-secreted sEV and examined the dominant components. The over-expression of the miR-382 in MG63 cell and its progression of osteogenic differentiation were investigated by qRT-PCR, western blot and alizarin red staining. The interaction between miR-382 and SLIT2 was confirmed by dual-luciferase assay. The role of SLIT2 was also confirmed through up-regulation in MG63 cell, and the osteogenic differentiation-associated gene and protein were tested. Results According to bioinformatic analysis, a series of differential expressed genes between persons with high or low BMD were compared. After internalization of hBMSC-sEV in MG63 cells, we observed that the ability of osteogenic differentiation was significantly enhanced. Similarly, after up-regulation of miR-382 in MG63 cells, osteogenic differentiation was also promoted. According to the dual-luciferase assay, the targeting function of miR-382 in SLIT2 was demonstrated. Moreover, the benefits of hBMSC-sEV in osteogenesis were abrogated through up-regulation of SLIT2. Conclusion Our study provided evidence that miR-382-contained hBMSC-sEV held great promise in osteogenic differentiation in MG63 cells after internalization by targeting SLIT2, which can be served as molecular targets to develop effective therapy.

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“…10 Recent data demonstrate that exosomes derived from osteoblasts, MSCs, osteoclasts and macrophages have therapeutic potential in osteoporosis and regenerative medicine. 4,11,12 Osteoblasts have been shown to communicate with other cell phenotypes through secretion of exosomes 13 and exosome-derived microRNAs exhibit a potential to direct osteogenesis and osteoclastogenesis. 14,15 However, there is a gap in the literature regarding the effects of preosteoblast-derived exosomes on bone marrow macrophages and bone remodelling dynamics.…”

Section: Introductionmentioning

confidence: 99%

“…They offer therapeutic advantages including biocompatibility, reduced immunogenicity and transportation of cargo contents without degradation due to the nature of the exosome bilipid capsule 10 . Recent data demonstrate that exosomes derived from osteoblasts, MSCs, osteoclasts and macrophages have therapeutic potential in osteoporosis and regenerative medicine 4,11,12 …”

Section: Introductionmentioning

confidence: 99%

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The effects of preosteoblast‐derived exosomes on macrophages and bone in mice

Hakki,

Batoon,

Koh

et al. 2023

J Cellular Molecular Medi

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The effect of preosteoblast‐derived exosomes on bone marrow macrophages (BMMΦ) and calvarial osteoblasts (cOB) was evaluated in vitro, and bone formation studies were performed in vivo in mice. Preosteoblastic MC3T3‐E1 clone 4 (MC4) cell‐derived exosomes (MC4exo) were characterized with particle tracking, transmission electron microscopy and western blot analysis to validate size, number, shape and phenotypic exosome markers. Exosomes pre‐labelled with PKH67 were incubated with BMMΦ and phagocytosis of exosomes was confirmed. To examine the effect of MC4exo on macrophage polarization, BMMΦ were treated with MC4exo and the expression of pro‐ and anti‐inflammatory cytokines was determined by qPCR. MC4exo treatment upregulated mRNA expression of Cd86, Il1β, Ccl2, Rankl and Nos, and downregulated Cd206, Il10 and Tnfα, suggesting a shift towards pro‐inflammatory ‘M1‐like’ macrophage polarization. Combination of RANKL and MC4exo increased osteoclast differentiation of BMMΦ in comparison to RANKL alone as analysed by TRAP staining. MC4exo treatment showed no significant effect on calvarial osteoblast mineralization. For in vivo studies, intratibial inoculation of MC4exo (2 × 109 particles in PBS, n = 12) and vehicle control (PBS only, n = 12) was performed in C57Bl/6 mice (8 weeks, male). Micro‐CT analyses of the trabecular and cortical bone compartments were assessed at 4 weeks post‐injection. Tibial sections were stained for TRAP activity to determine osteoclast presence and immunofluorescence staining was performed to detect osteocalcin (Ocn), osterix (Osx) and F4/80 expression. Intratibial inoculation of MC4exo increased the diaphyseal bone mineral density and trabecular bone volume fraction due to increased trabecular number. This increase in bone was accompanied by a reduction in bone marrow macrophages and osteoclasts at the experimental endpoint. Together, these findings suggest that preosteoblast‐derived exosomes enhanced bone formation by influencing macrophage responses.

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Stem Cell-derived Exosomal MicroRNA as Therapy for Vascular Age-related Diseases

Cited by 8 publications

References 100 publications

Stem Cell-Derived Extracellular Vesicles in the Treatment of Cardiovascular Diseases

Stem Cell-Derived Extracellular Vesicles in the Treatment of Cardiovascular Diseases

Bone marrow mesenchymal stem cell-derived exosomal microRNA-382 promotes osteogenesis in osteoblast via regulation of SLIT2

The effects of preosteoblast‐derived exosomes on macrophages and bone in mice

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