Extracellular vesicles derived from neural EGFL-Like 1-modified mesenchymal stem cells improve acellular bone regeneration via the miR-25-5p-SMAD2 signaling axis

Lan, Yanhua; Xie, Hujun; Jin, Qianrui; Zhao, Xiaomin; Shi, Yang; Zhou, Yanyan; Hu, Zihe; Ye, Yi; Huang, Xiaoyuan; Sun, Yue; Chen, Zhuo; Xie, Zhijian

doi:10.1016/j.bioactmat.2022.01.019

Cited by 26 publications

(21 citation statements)

References 77 publications

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“…Zhang et al used 3D printing to fabricate custom nano-hydroxyapatite/poly-ε-caprolactone (nHP) scaffolds in a rat calvarial defect model using umbilical cord MSC-derived exosomes (UCMSC-exos) encapsulated injectable hyaluronic acid hydrogels that completely filled the pore structure of nHP scaffolds, and it was found that these engineered UCMSC-exos could promote cranial defect repair in vivo and had a good proangiogenic effect in vitro [ 118 ]. In addition, based on Neural EGFL-like 1 (Nell1) as an exocrine protein associated with craniosynostosis to promote the osteogenic differentiation of BMSCs, Lan et al modified BMSC-derived cells with Nell1 gene extracellular vesicles (Nell1/EVs), constructing an extracellular vesicle-hydrogel composite system (3D-Nell1/EV-hydrogel system) [ 119 ]. The results confirmed that Nell1/EVs could induce stem cells to differentiate into osteoblasts by downregulating miR-25-5p, which can inhibit osteogenesis by targeting Smad2 and inhibiting the activation of the SMAD and ERK signaling pathways.…”

Section: Technologies For Engineering Mscs and Msc-exosmentioning

confidence: 99%

“…The results confirmed that Nell1/EVs could induce stem cells to differentiate into osteoblasts by downregulating miR-25-5p, which can inhibit osteogenesis by targeting Smad2 and inhibiting the activation of the SMAD and ERK signaling pathways. In addition, the 3D-Nell1/EV-hydrogel system could realize the slow and sustained release of EVs in the bone defect area and the preservation of high concentrations, which can effectively promote the repair of large-scale bone defects in animals [ 119 ].…”

Section: Technologies For Engineering Mscs and Msc-exosmentioning

confidence: 99%

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Research progress of engineered mesenchymal stem cells and their derived exosomes and their application in autoimmune/inflammatory diseases

Zhu

Yang

et al. 2023

Stem Cell Res Ther

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Autoimmune/inflammatory diseases affect many people and are an important cause of global incidence and mortality. Mesenchymal stem cells (MSCs) have low immunogenicity, immune regulation, multidifferentiation and other biological characteristics, play an important role in tissue repair and immune regulation and are widely used in the research and treatment of autoimmune/inflammatory diseases. In addition, MSCs can secrete extracellular vesicles with lipid bilayer structures under resting or activated conditions, including exosomes, microparticles and apoptotic bodies. Among them, exosomes, as the most important component of extracellular vesicles, can function as parent MSCs. Although MSCs and their exosomes have the characteristics of immune regulation and homing, engineering these cells or vesicles through various technical means, such as genetic engineering, surface modification and tissue engineering, can further improve their homing and other congenital characteristics, make them specifically target specific tissues or organs, and improve their therapeutic effect. This article reviews the advanced technology of engineering MSCs or MSC-derived exosomes and its application in some autoimmune/inflammatory diseases by searching the literature published in recent years at home and abroad.

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Section: Technologies For Engineering Mscs and Msc-exosmentioning

confidence: 99%

Section: Technologies For Engineering Mscs and Msc-exosmentioning

confidence: 99%

Research progress of engineered mesenchymal stem cells and their derived exosomes and their application in autoimmune/inflammatory diseases

Zhu

Yang

et al. 2023

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…In addition, it was demonstrated that the 3D hydrogel system assembled with Nell1 /EVs is beneficial for acellular bone regeneration on calvarial defect rat model, evidenced with better bone formation in the animals. Therefore, Nell1 /EVs is a promising strategy for bone defect healing with favourable osteogenic capability through regulation of miR-25-5p/Smad2 signalling [ 214 ].…”

Section: Microrna Regulation Of the Smad Cascadesmentioning

confidence: 99%

Post-Transcriptional Regulatory Crosstalk between MicroRNAs and Canonical TGF-β/BMP Signalling Cascades on Osteoblast Lineage: A Comprehensive Review

Loh

Norman

Lai

et al. 2023

IJMS

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MicroRNAs (miRNAs) are a family of small, single-stranded, and non-protein coding RNAs about 19 to 22 nucleotides in length, that have been reported to have important roles in the control of bone development. MiRNAs have a strong influence on osteoblast differentiation through stages of lineage commitment and maturation, as well as via controlling the activities of osteogenic signal transduction pathways. Generally, miRNAs may modulate cell stemness, proliferation, differentiation, and apoptosis by binding the 3′-untranslated regions (3′-UTRs) of the target genes, which then can subsequently undergo messenger RNA (mRNA) degradation or protein translational repression. MiRNAs manage the gene expression in osteogenic differentiation by regulating multiple signalling cascades and essential transcription factors, including the transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP), Wingless/Int-1(Wnt)/β-catenin, Notch, and Hedgehog signalling pathways; the Runt-related transcription factor 2 (RUNX2); and osterix (Osx). This shows that miRNAs are essential in regulating diverse osteoblast cell functions. TGF-βs and BMPs transduce signals and exert diverse functions in osteoblastogenesis, skeletal development and bone formation, bone homeostasis, and diseases. Herein, we highlighted the current state of in vitro and in vivo research describing miRNA regulation on the canonical TGF-β/BMP signalling, their effects on osteoblast linage, and understand their mechanism of action for the development of possible therapeutics. In this review, particular attention and comprehensive database searches are focused on related works published between the years 2000 to 2022, using the resources from PubMed, Google Scholar, Scopus, and Web of Science.

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“…Wei (195) et al proposed that BMSCs-Exo derived from different stages of osteogenic induction could exert a sustained anti-inflammatory effect during osteogenesis, up-regulate genes associated with osteogenesis at the early stage, and promote MSCs migration at the later stage. EVs derived from neural EGFL-like 1 modified BMSCs were more capable of stimulating BMSCs osteogenesis due to the downregulation of miR-25-5p (196). Huang (197) et al demonstrated that EVs derived from BMP2overexpressing BMSCs preserved the essential physical and biochemical characteristics of BMSCs-EVs but showed greater bone regeneration capability in a rat calvarial defect model.…”

Section: Role Of Mscs-evs In Periodontal Regenerationmentioning

confidence: 99%

The role of extracellular vesicles in periodontitis: pathogenesis, diagnosis, and therapy

et al. 2023

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Periodontitis is a prevalent disease and one of the leading causes of tooth loss. Biofilms are initiating factor of periodontitis, which can destroy periodontal tissue by producing virulence factors. The overactivated host immune response is the primary cause of periodontitis. The clinical examination of periodontal tissues and the patient’s medical history are the mainstays of periodontitis diagnosis. However, there is a lack of molecular biomarkers that can be used to identify and predict periodontitis activity precisely. Non-surgical and surgical treatments are currently available for periodontitis, although both have drawbacks. In clinical practice, achieving the ideal therapeutic effect remains a challenge. Studies have revealed that bacteria produce extracellular vesicles (EVs) to export virulence proteins to host cells. Meanwhile, periodontal tissue cells and immune cells produce EVs that have pro- or anti-inflammatory effects. Accordingly, EVs play a critical role in the pathogenesis of periodontitis. Recent studies have also presented that the content and composition of EVs in saliva and gingival crevicular fluid (GCF) can serve as possible periodontitis diagnostic indicators. In addition, studies have indicated that stem cell EVs may encourage periodontal regeneration. In this article, we mainly review the role of EVs in the pathogenesis of periodontitis and discuss their diagnostic and therapeutic potential.

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Extracellular vesicles derived from neural EGFL-Like 1-modified mesenchymal stem cells improve acellular bone regeneration via the miR-25-5p-SMAD2 signaling axis

Cited by 26 publications

References 77 publications

Research progress of engineered mesenchymal stem cells and their derived exosomes and their application in autoimmune/inflammatory diseases

Research progress of engineered mesenchymal stem cells and their derived exosomes and their application in autoimmune/inflammatory diseases

Post-Transcriptional Regulatory Crosstalk between MicroRNAs and Canonical TGF-β/BMP Signalling Cascades on Osteoblast Lineage: A Comprehensive Review

The role of extracellular vesicles in periodontitis: pathogenesis, diagnosis, and therapy

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