Angiogenic activity of cytochalasin B-induced membrane vesicles of human mesenchymal stem cells

Gomzikova, M.; Zhuravleva, M.; Vorobev, V.; Salafutdinov, I.; Laikov, A.; Kletukhina, S.; Martynova, E.; Tazetdinova, L.; Ntekim, A.; Khaiboullina, S.; Rizvanov, A.

doi:10.1101/646398

bioRxiv · 10.1101/646398

Angiogenic activity of cytochalasin B-induced membrane vesicles of human mesenchymal stem cells

Gomzikova, M.·Zhuravleva, M.·Vorobev, V.·Salafutdinov, I.·Laikov, A.·Kletukhina, S.·Martynova, E.·Tazetdinova, L.·Ntekim, A.·Khaiboullina, S.·Rizvanov, A.

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Abstract

BackgroundThe 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 cells (MSCs) derived CIMVs (CIMVs-MSCs) remains unknown.\n\nObjectivesThe objectives of this study were to analyzed the morphology, size distribution, molecular composition and angiogenic properties of CIMVs-MSCs.\n\nMethodsThe 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 in vivo approach of subcutaneous implantation of CIMVs-MSCs in mixture with Matrigel matrix.\n\nResultsHuman CIMVs-MSCs retain parental MSCs content such as growth factors, cytokines, chemokines: EGF, FGF-2, Eotaxin, TGF-, G-CSF, Flt-3L, GM-CSF, Fractalkine, IFN2, IFN-{gamma}, 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-, TNF-{beta}, 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.\n\nConclusionsHuman 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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Gomzikova, M., Zhuravleva, M., Vorobev, V., Salafutdinov, I., Laikov, A., Kletukhina, S., Martynova, E., Tazetdinova, L., Ntekim, A., Khaiboullina, S., Rizvanov, A.. 2019-05-22. Angiogenic activity of cytochalasin B-induced membrane vesicles of human mesenchymal stem cells. https://doi.org/10.1101/646398

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