Human mesenchymal stromal cells and derived extracellular vesicles: Translational strategies to increase their proangiogenic potential for the treatment of cardiovascular disease

Nazari-Shafti, Timo Z.; Neuber, Sebastian; Duran, Ana G.; Xu, Zhifeng; Beltsios, Eleftherios T.; Seifert, Martina; Falk, Volkmar; Stamm, Christof

doi:10.1002/sctm.19-0432

Cited by 30 publications

(27 citation statements)

References 165 publications

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“…Therefore, they can be manipulated and applied to establish novel cell-free therapeutic approaches for treatment of a variety of pathological conditions, distinct from those induced by viruses mentioned previously. In comparison with their donor cells, MSC-EVs offer more stable events, with diminished safety risks of microvasculature occlusion [ 44 , 45 ]. The author conclude that MSC-EVs possesses most of the functional and therapeutic activities recognized to their original cells during the decades of their employment.…”

Section: Discussionmentioning

confidence: 99%

News About the Extracellular Vesicles from Mesenchymal Stem Cells: Functions, Therapy and Protection from COVID-19

Meldolesi

2021

Journal of Experimental Pathology

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This is a Commentary of a review about extracellular vesicles of immune cells published two years ago in Clinical and Experimental Immunology, a prestigious journal of the field. The aim is to establish whether, and to what extent, results in scientific area of the review have been extended and strengthened by innovative findings of considerable interest. The analysis of the recently published results has revealed that in various areas of the review developments have occurred. However, innovative findings have been only about the extracellular vesicles secreted by mesenchymal stem cells, usually indicated as MSC-EVs. Based on these findings, the Commentary has been focused on recent MSC-EVs findings presented in three Sections dealing with 1. recently appeared, relevant functions of the latter vesicles; 2. therapeutic processes developed according well known criteria, however innovative in many respects; and 3. protection of COVID-19 disease patients from organ lesions induced by the specific virus, SARS-CoV-2, during the disease. As everybody knows, the COVID-19 pandemic started at the end of 2019, thus after the publication of the aforementioned review. Data of Section 3 are therefore innovative, of great potential interest also at the clinical level, applied by translational medicine to various organs, from lung to brain, heart, kidney, immune and other cells. In view of its relevance, the author expects that research and medical use of MSC-EV, active at present, will be further developed, acquiring additional relevance in the near future.

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Section: Discussionmentioning

confidence: 99%

News About the Extracellular Vesicles from Mesenchymal Stem Cells: Functions, Therapy and Protection from COVID-19

Meldolesi

2021

Journal of Experimental Pathology

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“…Acting as the crucial mediators of MSC-exosomes, miRNAs can provide sustained therapeutic effect and fundamental alterations of the local microenvironment, making it an ideal therapeutic biomolecule [31]. Many researches have validated the role of miRNAs in exosomes in various types of cells [32,33]. In order to further explore how HUMSCexosomes affects the corneal epithelial cells, we consulted GEO dataset and combined with bioinformatic analysis methods to analyze the content composition of exosomal miRNAs, and transcriptome sequencing was performed to identify the DEGs in HUMSC-exosomes treated HCECs compared to untreated condition.…”

Section: Discussionmentioning

confidence: 99%

Umbilical Cord Mesenchymal Stem Cells-derived Exosomes Deliver Mir-21 to Accelerate Corneal Epithelial Wound Healing Through PTEN/PI3K/Akt pathway

Li¹,

Liu²,

Zhang³

et al. 2021

Preprint

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BackgroundRapid restoration of corneal epithelium integrity after injury is particularly important for preserving corneal transparency and vision. Mesenchymal stem cells (MSCs) can be taken into account as the promising regenerative therapeutics for improvement of wound healing processes based on the variety of the effective components. The extracellular vesicles form MSCs, especially exosomes, has been considered as important paracrine mediators though transferring microRNAs into recipient cell. This study investigated the mechanism of human umbilical cord MSC-derived exosomes (HUMSC-exosomes) on corneal epithelial wound healing.MethodsExosomes extracted from HUMSCs were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Corneal fluorescein staining and histological staining were evaluated in a corneal mechanical wound model. Changes in HCECs proliferation after HUMSC-exosomes or miR-21 mimic treatment were evaluated by CCK-8 and EdU assays, while migration was assessed by in vitro scratch wound assay. Full-length transcriptome sequencing was performed to identify the differentially expressed genes associated with HUMSC-exosomes treatment, followed by validation via real-time PCR and Western blot.ResultsThe exosomes derived from HUMSCs can significantly promote corneal epithelial cells proliferation, migration in vitro and accelerate corneal epithelial wound healing in vivo. Similar effects were obtained after miR-21 transfection, while the beneficial effects of HUMSC-exosomes were partially negated by miR-21 knockdown. Results also show that the benefits are associated with decreased PTEN level and activated the PI3K/Akt signaling pathway in HCECs.ConclusionsHUMSC-exosomes could accelerate the recovery of corneal epithelial wounds though restraining PTEN by transferring miR-21, and may represent a promising novel therapeutic agent for corneal wound repair.

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“…EVs are enclosed phospholipid bilayer vesicles releasing from almost cells with the key roles in intracellular communication and physiological as well as pathological processes [ 16 ]. Recently, EVs have attracted much attention as cell-based therapeutic agents due to their ability transfer therapeutic biomolecules and facilitating injury repair [ 17 , 18 ]. A class of EVs is exosomes that facilitate ischemic diseases recovery and angiogenesis through angiogenesis regulatory factors into damaged tissues [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Application of stem cell-derived exosomes in ischemic diseases: opportunity and limitations

Babaei

Rezaie

2021

J Transl Med

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Ischemic diseases characterized by an insufficient blood flow that leads to a decrease in oxygen and nutrient uptake by cells have emerged as an important contributor to both disability and death worldwide. Up-regulation of angiogenesis may be a key factor for the improvement of ischemic diseases. This article searched articles in PubMed with the following keywords: stem cells, exosomes, angiogenesis, ischemic diseases either alone or in grouping form. The most relevant selected items were stem cell-derived exosomes and ischemic diseases. A growing body of evidence indicates that stem cells produce exosomes, which is the novel emerging approach to cell-to-cell communication and offers a new standpoint on known therapeutic strategies of ischemic diseases. Exosomes transport biological molecules such as many types of proteins, RNAs, DNA fragments, signaling molecules, and lipids between cells. Different stem cells release exosomes representing beneficial effects on ischemic diseases as they promote angiogenesis both in vitro and in vivo experiments. Application of exosomes for therapeutic angiogenesis opened new opportunities in the regenerative medicine, however, some limitations regarding exosomes isolation and application remain concerned. In addition, most of the experiments were conducted in preclinical and therefore translation of these results from bench to bed requires more effort in this field. Exosomes from stem cells are a promising tool for the treatment of ischemic diseases. In addition, translation of pre-clinic results into clinic needs further studies in this field.

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Human mesenchymal stromal cells and derived extracellular vesicles: Translational strategies to increase their proangiogenic potential for the treatment of cardiovascular disease

Cited by 30 publications

References 165 publications

News About the Extracellular Vesicles from Mesenchymal Stem Cells: Functions, Therapy and Protection from COVID-19

News About the Extracellular Vesicles from Mesenchymal Stem Cells: Functions, Therapy and Protection from COVID-19

Umbilical Cord Mesenchymal Stem Cells-derived Exosomes Deliver Mir-21 to Accelerate Corneal Epithelial Wound Healing Through PTEN/PI3K/Akt pathway

Application of stem cell-derived exosomes in ischemic diseases: opportunity and limitations

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