The Angiogenic Potential of Adipose Mesenchymal Stem Cell-derived Extracellular Vesicles is modulated by Basic Fibroblast Growth Factor

Lopatina, Tatiana; Mazzeo, Aurora; Bruno, Stefania; Tetta, Ciro; Калинина, Н.И.; Romagnoli, Renato; Salizzoni, Mauro; Porta, Massimo; Camussi, Giovanni

doi:10.4172/2157-7633.1000245

Cited by 6 publications

(13 citation statements)

References 33 publications

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“…Our data corroborate results published by Gangadaran et al where MSCs-derived EVs increased cellular migration, proliferation, endothelial tube formation in vitro, and enhanced angiogenesis in ischemic limb in vivo [8]. In addition, Lopatina et al reported that MSCs-derived EVs could induce the formation of vessel-like structures in vitro and in vivo after the subcutaneous injection in mixture with Matrigel Matrix and human microvascular endothelial cells [37]. We believe that the angiogenic capacity of CIMVs-MSCs depends on growth factors present in their content.…”

Section: Discussionsupporting

confidence: 92%

Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells

Gomzikova

Zhuravleva

Vorobev

et al. 2019

Cells

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The cytochalasin B-induced membrane vesicles (CIMVs) are suggested to be used as a vehicle for the delivery of therapeutics. However, the angiogenic activity and therapeutic potential of human mesenchymal stem/stromal cells (MSCs) derived CIMVs (CIMVs-MSCs) remains unknown. Objectives: The objectives of this study were to analyze the morphology, size distribution, molecular composition, and angiogenic properties of CIMVs-MSCs. Methods: The morphology of CIMVs-MSC was analyzed by scanning electron microscopy. The proteomic analysis, multiplex analysis, and immunostaining were used to characterize the molecular composition of the CIMVs-MSCs. The transfer of surface proteins from a donor to a recipient cell mediated by CIMVs-MSCs was demonstrated using immunostaining and confocal microscopy. The angiogenic potential of CIMVs-MSCs was evaluated using an in vivo approach of subcutaneous implantation of CIMVs-MSCs in mixture with Matrigel matrix. Results: Human CIMVs-MSCs retain parental MSCs content, such as growth factors, cytokines, and chemokines: EGF, FGF-2, Eotaxin, TGF-α, G-CSF, Flt-3L, GM-CSF, Fractalkine, IFNα2, IFN-γ, GRO, IL-10, MCP-3, IL-12p40, MDC, IL-12p70, IL-15, sCD40L, IL-17A, IL-1RA, IL-1a, IL-9, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MIP_1a, MIP-1b, TNF-α, TNF-β, VEGF. CIMVs-MSCs also have the expression of surface receptors similar to those in parental human MSCs (CD90+, CD29+, CD44+, CD73+). Additionally, CIMVs-MSCs could transfer membrane receptors to the surfaces of target cells in vitro. Finally, CIMVs-MSCs can induce angiogenesis in vivo after subcutaneous injection into adult rats. Conclusions: Human CIMVs-MSCs have similar content, immunophenotype, and angiogenic activity to those of the parental MSCs. Therefore, we believe that human CIMVs-MSCs could be used for cell free therapy of degenerative diseases.

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Section: Discussionsupporting

confidence: 92%

Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells

Gomzikova

Zhuravleva

Vorobev

et al. 2019

Cells

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“…This confirms that ASC and MSC EVs have both pro-angiogenic properties [11,24] and are able to restore tube formation ability in endothelial cells damaged by high glucose conditioning. These biological effects are consistent with previous observation that MSC EVs and ASC EVs contain several proangiogenic factors [11][12][13][14][24][25][26][27] and miRNAs [20][21][22]46]. …”

Section: Resultssupporting

confidence: 93%

“…Moreover, they carry matrix metalloproteinases (MMPs) that play an important role in angiogenesis by facilitating endothelial cell migration and by promoting activation of angiogenic growth factors and other signaling molecules [25]. It has been also shown that the proangiogenic content of ASC EVs is modulated by the microenvironment, for example in vitro by the addition of different growth factors [26], or in vivo by obesity, which reduces their pro-angiogenic potential [27].…”

Section: Introductionmentioning

confidence: 99%

Protective Role of Stem Cell Derived Extracellular Vesicles in an In Vitro Model of Hyperglycemia-Induced Endothelial Injury

Gai¹,

Gomez²,

Tetta³

et al. 2017

J Cell Sci Ther

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Background: Adipose and bone marrow derived mesenchymal stem cells are two populations of multipotent adult stem cells with immunosuppressive, anti-inflammatory, and regenerative properties. It has been previously described that extracellular vesicles (EVs) derived from stem cells possess pro-regenerative and pro-angiogenic abilities. Hyperglycemia is a pathological condition affecting diabetic patients. Long term effects of hyperglycemia are endothelial dysfunction and vascular lesions leading to diabetic microangiopathy.

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“…We found in our study that EVs released from ASCs carried several angiogenic factors such as c-kit, MFG-E8, SCF, APRIL, artemin, angiopoietin-like factor and the matrix metalloproteinase MMP-20 which facilitated endothelial cell migration [47]. Furthermore, several pro-angiogenic miRNAs including miR-17, miR-21, miR-126, miR-130a, miR-210 and miR-296 were also discovered to be enriched in these EVs [48]. Interestingly, we also observed that the microenvironment plays an important role in modulation of EV cargo and their biological activity.…”

Section: Evs In Angiogenic Tissue Regenerationmentioning

confidence: 60%

“…In fact, the invasiveness of EV-treated endothelial cells was significantly reduced by Batimastat, an inhibitor of matrix metalloproteinases. In contrast, stimulation of ASCs with bFGF induced the release of vesicles which exhibited stabilizing effects on vessel growth [48] (Fig. 2D).…”

Section: Evs In Angiogenic Tissue Regenerationmentioning

confidence: 94%

Extracellular vesicles as new players in angiogenesis

Kholia

Ranghino

Garnieri

et al. 2016

Vascular Pharmacology

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Growing evidence suggests that small vesicles actively released from cells may encapsulate transcriptional regulators and RNA molecules. Their ability to interact with neighbouring cells and/or with distant cells through biological fluids, makes them a medium through which intercellular exchange of information can happen. Recently, membrane vesicles, which include exosomes and microvesicles, gained a place amongst the vast group of angiogenic mediators. In the present review we discuss the potential relevance of these vesicles in physiological and pathological situations of angiogenesis as well as their mechanism of action.

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The Angiogenic Potential of Adipose Mesenchymal Stem Cell-derived Extracellular Vesicles is modulated by Basic Fibroblast Growth Factor

Cited by 6 publications

References 33 publications

Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells

Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells

Protective Role of Stem Cell Derived Extracellular Vesicles in an In Vitro Model of Hyperglycemia-Induced Endothelial Injury

Extracellular vesicles as new players in angiogenesis

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