Human peripheral blood‑derived exosomes for microRNA delivery

Kang, Jiyoung; Park, Hyewon; Kim, Hyoeun; Mun, Dasom; Yun, Nuri; Joung, Boyoung

doi:10.3892/ijmm.2019.4150

Cited by 36 publications

(25 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, miR-21 mimic-loaded exosomes enhanced fibrosis in the mouse model of myocardial infarction. 52 Similarly, a study of renal fibrosis reported that treatment with miR-21 significantly aggravated the TGF-β-induced epithelial fibroblast phenotype. 53 Thus, overexpression of mir-21 may tend to fibrosis.…”

Section: Discussionmentioning

confidence: 97%

<p>MicroRNA-21-3p Engineered Umbilical Cord Stem Cell-Derived Exosomes Inhibit Tendon Adhesion</p>

Yao¹,

Li²,

Wang³

et al. 2020

JIR

View full text Add to dashboard Cite

As a common complication of tendon injury, tendon adhesion is an unresolved problem in clinical work. The aim of this study was to investigate whether human umbilical cord mesenchymal stem cell-derived exosomes (HUMSC-Exos), one of the most promising new-generation cell-free therapeutic agents, can improve tendon adhesion and explore potential-related mechanisms. Methods: The rat Achilles tendon injury adhesion model was constructed in vivo, and the localization of HUMSC-Exos was used to evaluate the tendon adhesion. Rat fibroblast cell lines were treated with transforming growth factor β1 (TGF-β1) and/or HUMSC-Exos in vitro, and cell proliferation, apoptosis and gene expression were measured. MicroRNA (miRNA) sequencing and quantitative PCR (qPCR) analysis confirmed differential miRNAs. A specific miRNA antagonist (antagomir-21a-5p) was used to transform HUMSC-Exos and obtain modified exosomes to verify its efficacy and related mechanism of action. Results: In this study, we found HUMSC-Exos reduced rat fibroblast proliferation and inhibited the expression of fibrosis genes: collagen III (COL III) and α-smooth muscle actin (α-SMA) in vitro. In the rat tendon adhesion model, topical application of HUMSC-Exos contributed to relief of tendon adhesion. Specifically, the fibrosis and inflammationrelated genes were simultaneously inhibited by HUMSC-Exos. Further, miRNA sequencing of HUMSCs and HUMSC-Exos showed that miR-21a-3p was expressed at low abundance in HUMSC-Exos. The antagonist targeting miR-21a-3p was recruited for treatment of HUMSCs, and harvested HUMSC-Exos, which expressed low levels of miR-21a-3p, and expanded the inhibition of tendon adhesion in subsequent in vitro experiments. Conclusion: Our results indicate that HUMSC-Exos may manipulate p65 activity by delivering low-abundance miR-21a-3p, ultimately inhibiting tendon adhesion. The findings may be promising for dealing with tendon adhesion.

show abstract

Section: Discussionmentioning

confidence: 97%

<p>MicroRNA-21-3p Engineered Umbilical Cord Stem Cell-Derived Exosomes Inhibit Tendon Adhesion</p>

Yao¹,

Li²,

Wang³

et al. 2020

JIR

View full text Add to dashboard Cite

show abstract

“…Several EV formulations have been enriched using transfection agents or membranepermeabilizing strategies and evaluated in the context of cardiovascular applications to decrease cardiac fibrosis, modulate the inflammatory response and to increase angiogenesis (Table 1). For example, miRNA-21-5p has a critical role in the development of fibrosis after MI, regulating several gene targets including SMAD family member 7 (Smad7), sprout RTK signalling antagonist 1 and phosphatase and tensin homolog (PTEN) 141 . Human peripheral blood-derived EVs enriched for miR-21 inhibitors reduced fibrosis in a mouse model of MI as compared to non-modified EVs.…”

Section: 22-post-isolation Methodsmentioning

confidence: 99%

Native and bioengineered extracellular vesicles for cardiovascular therapeutics

et al. 2020

View full text Add to dashboard Cite

Extracellular vesicles (EVs) are a heterogeneous group of natural particles with relevance for the treatment of cardiovascular diseases. The endogenous properties of these vesicles allow them to survive in the extracellular space, bypass biological barriers and deliver their biologically active molecular cargo to recipient cells. Moreover, EVs can be engineered to enhance their stability, bioactivity, presentation and capacity for on target binding at both cell type and tissue levels. The therapeutic potential of native (i.e., EVs that were not modified via donor cell or direct modulation) and engineered (i.e. EVs that were modified either pre-or post-isolation or whose pharmacokinetics/presentation was altered using engineering methodologies EVs is still limitedly explored in the context of cardiovascular diseases. Efforts to tap into the therapeutic potential of EVs will require innovative approaches and a comprehensive integration of knowledge gathered from decades of molecular compound delivery. In this review, we outline the endogenous properties of EVs that make them natural delivery agents as well as those features that can be improved using bioengineering approaches. We also discuss the therapeutic applications of native and engineered EVs for cardiovascular applications and examine the opportunities and challenges that need to be addressed to advance this research area with an emphasis on clinical translation. Key points• EVs secreted from stem/progenitor cells as well as differentiated somatic cells have regenerative properties in the context of myocardial infarction, ischemic limb, chronic wounds and stroke.

show abstract

“…Over the last decade, miRNAs have emerged as key regulators of several cellular processes, including angiogenesis, and certain miRNAs, such as miR-132, miR-126, miR-451a, miR-494-3p, miR-16a-5p and miR-23a-3p, have been shown to play key roles in the vasculature in both endothelial and perivascular cells ( 11 , 12 ). In addition, previous studies have demonstrated that EXs contain a large number of miRNAs, and EXs may deliver these miRNAs to their target cells ( 13 - 15 ). It was previously reported that DC infiltration is significantly increased in the infarcted myocardium and plays an important role in angiogenesis and cardiac healing after MI ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Dendritic cell‑derived exosomal miR‑494‑3p promotes angiogenesis following myocardial infarction

Zhang

Yuan

et al. 2020

Int J Mol Med

View full text Add to dashboard Cite

Infiltration by dendritic cells (dcs) is markedly increased in the infarcted area following myocardial infarction (MI), and dc ablation has been shown to impair angiogenesis in mice post-MI. Exosomes (EXs) have long been known to act as messengers between cells; however, whether EXs derived from dcs can enhance myocardial angiogenesis post-MI remains unknown. The aim of the present study was to elucidate whether EXs derived from dcs induce myocardial angiogenesis via paracrine signaling post-MI. In vitro, suspensions of mouse bone marrow-derived dcs (BMdcs) were incubated with the supernatant of necrotic or normal cultured HL-1 myocardial cells (as the MI or control group, respectively) for 24 h. EXs isolated from the supernatant of BMdcs were termed dEXs, which were added to primary cultures of rat cardiac microvascular endothelial cells (cMEcs), and angiogenesis was evaluated by measuring tube formation and vascular endothelial growth factor (VEGF) expression. In vivo, different groups of dEXs were injected into the infarcted myocardium of MI model mice. Then, angiogenesis was evaluated by measuring the number of vessels and the expression of VEGF and cd31 in the infarcted myocardium using immunohistochemistry. Moreover, the expression profile of microRNAs (miRNAs or miRs) in splenic dcs of MI model mice was analyzed by Affymetrix miRNA 4.0 chip assays, then certified in DEXs by reverse transcription-quantitative PcR analysis. Finally, miRNA-loaded dEXs were used to induce tube formation by cMEcs and angiogenesis in MI model mice. It was observed that, compared with the control group, DEXs from the MI group significantly upregulated the expression of VEGF in cMEcs, enhanced tube formation by cMEcs, and upregulated the expression of VEGF and cd31 in the infarcted myocardium of MI model mice. miR-494-3p and miR-16a-5p, which are associated with angiogenesis, were significantly upregulated in splenic DCs of MI model mice by Affymetrix miRNA 4.0 chip assays, miR-494-3p was significantly upregulated and highly enriched in dEXs from the MI group compared with the control, and dEX-miR-494-3p enhanced tube formation by cMEcs and angiogenesis in mice post-MI. These results suggest that miR-494-3p may be secreted from dcs via EXs and promotes angiogenesis post-MI. These findings indicate a novel DEX-based approach to the treatment of MI.

show abstract

Human peripheral blood‑derived exosomes for microRNA delivery

Cited by 36 publications

References 46 publications

<p>MicroRNA-21-3p Engineered Umbilical Cord Stem Cell-Derived Exosomes Inhibit Tendon Adhesion</p>

<p>MicroRNA-21-3p Engineered Umbilical Cord Stem Cell-Derived Exosomes Inhibit Tendon Adhesion</p>

Native and bioengineered extracellular vesicles for cardiovascular therapeutics

Dendritic cell‑derived exosomal miR‑494‑3p promotes angiogenesis following myocardial infarction

Contact Info

Product

Resources

About