Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells
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 objective...
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2019-12-01
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author | Marina O. Gomzikova Margarita N. Zhuravleva Vyacheslav V. Vorobev Ilnur I. Salafutdinov Alexander V. Laikov Sevindzh K. Kletukhina Ekaterina V. Martynova Leysan G. Tazetdinova Atara I. Ntekim Svetlana F. Khaiboullina Albert A. Rizvanov |
author_facet | Marina O. Gomzikova Margarita N. Zhuravleva Vyacheslav V. Vorobev Ilnur I. Salafutdinov Alexander V. Laikov Sevindzh K. Kletukhina Ekaterina V. Martynova Leysan G. Tazetdinova Atara I. Ntekim Svetlana F. Khaiboullina Albert A. Rizvanov |
author_sort | Marina O. Gomzikova |
collection | DOAJ |
description | 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<sup>+</sup>, CD29<sup>+</sup>, CD44<sup>+</sup>, CD73<sup>+</sup>). 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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spelling | doaj.art-b3ab731a9a504463a04439c27ca4423b2023-09-02T22:21:43ZengMDPI AGCells2073-44092019-12-01919510.3390/cells9010095cells9010095Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem CellsMarina O. Gomzikova0Margarita N. Zhuravleva1Vyacheslav V. Vorobev2Ilnur I. Salafutdinov3Alexander V. Laikov4Sevindzh K. Kletukhina5Ekaterina V. Martynova6Leysan G. Tazetdinova7Atara I. Ntekim8Svetlana F. Khaiboullina9Albert A. Rizvanov10Openlab “Gene and cell technologies”, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaOpenlab “Gene and cell technologies”, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaOpenlab “Gene and cell technologies”, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaOpenlab “Gene and cell technologies”, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaOpenlab “Gene and cell technologies”, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaOpenlab “Gene and cell technologies”, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaOpenlab “Gene and cell technologies”, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaOpenlab “Gene and cell technologies”, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaFaculty of Medicine and Health Sciences, University of Nottingham, Nottingham LE12 5RD, UKOpenlab “Gene and cell technologies”, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaOpenlab “Gene and cell technologies”, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaThe 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<sup>+</sup>, CD29<sup>+</sup>, CD44<sup>+</sup>, CD73<sup>+</sup>). 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.https://www.mdpi.com/2073-4409/9/1/95extracellular vesiclesmicrovesiclesmembrane vesiclescytochalasin bmesenchymal stem cellsangiogenesiscell-free therapy |
spellingShingle | Marina O. Gomzikova Margarita N. Zhuravleva Vyacheslav V. Vorobev Ilnur I. Salafutdinov Alexander V. Laikov Sevindzh K. Kletukhina Ekaterina V. Martynova Leysan G. Tazetdinova Atara I. Ntekim Svetlana F. Khaiboullina Albert A. Rizvanov Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells Cells extracellular vesicles microvesicles membrane vesicles cytochalasin b mesenchymal stem cells angiogenesis cell-free therapy |
title | Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells |
title_full | Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells |
title_fullStr | Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells |
title_full_unstemmed | Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells |
title_short | Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells |
title_sort | angiogenic activity of cytochalasin b induced membrane vesicles of human mesenchymal stem cells |
topic | extracellular vesicles microvesicles membrane vesicles cytochalasin b mesenchymal stem cells angiogenesis cell-free therapy |
url | https://www.mdpi.com/2073-4409/9/1/95 |
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