Mesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1
Abstract Mesenchymal stem cells/stromal cells (MSCs)-derived extracellular vesicles (EVs) mediate pro-regenerative effects in damaged ischemic tissues by regulating angiogenesis. MSCs-EVs modulate functions of cells including endogenous mature cells, progenitors and stem cells, resulting in restorat...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-024-02304-y |
| _version_ | 1797273381432721408 |
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| author | Anna Łabędź-Masłowska Luisa Vergori Sylwia Kędracka-Krok Elżbieta Karnas Sylwia Bobis-Wozowicz Małgorzata Sekuła-Stryjewska Michał Sarna Ramaroson Andriantsitohaina Ewa K. Zuba-Surma |
| author_facet | Anna Łabędź-Masłowska Luisa Vergori Sylwia Kędracka-Krok Elżbieta Karnas Sylwia Bobis-Wozowicz Małgorzata Sekuła-Stryjewska Michał Sarna Ramaroson Andriantsitohaina Ewa K. Zuba-Surma |
| author_sort | Anna Łabędź-Masłowska |
| collection | DOAJ |
| description | Abstract Mesenchymal stem cells/stromal cells (MSCs)-derived extracellular vesicles (EVs) mediate pro-regenerative effects in damaged ischemic tissues by regulating angiogenesis. MSCs-EVs modulate functions of cells including endogenous mature cells, progenitors and stem cells, resulting in restoration of blood flow. However, the mechanisms underlying such MSC-EV activity still remain poorly understood. The present study analyzes biological effects of bone marrow (BM) MSC-EVs on endothelial cells (ECs) in ischemic tissues both in in vitro and in vivo conditions and elucidates the molecular mechanisms underlying the tissue repair. MSC-EVs were isolated from murine BM-derived MSCs and their morphological, antigenic and molecular composition regarding protein and microRNA levels were evaluated to examine their properties. Global proteomic analysis demonstrated the presence in MSC-EVs of proteins regulating pro-regenerative pathways, including integrin α5 (Itgα5) and neuropilin-1 (NRP1) involved in lymphangiogenesis. MSC-EVs were also enriched in microRNAs regulating angiogenesis, TGF-β signaling and processes guiding cellular adhesion and interactions with extracellular matrix. The functional effects of MSC-EVs on capillary ECs in vitro included the increase of capillary-like tube formation and cytoprotection under normal and inflammatory conditions by inhibiting apoptosis. Notably, MSC-EVs enhanced also capillary-like tube formation of lymphatic ECs, which may be regulated by Itgα5 and NRP1. Moreover, in a mouse model of critical hind limb ischemia, MSC-EVs increased the recovery of blood flow in ischemic muscle tissue, which was accompanied with increased vascular density in vivo. This pro-angiogenic effect was associated with an increase in nitric oxide (NO) production via endothelial NO-synthase activation in ischemic muscles. Interestingly, MSC-EVs enhanced lymphangiogenesis, which has never been reported before. The study provides evidence on pro-angiogenic and novel pro-lymphangiogenic role of MSC-EVs on ECs in ischemic tissue mediated by their protein and miRNA molecular cargos. The results highlight Itgα5 and NRP1 carried by MSC-EVs as potential therapeutic targets to boost lymphangiogenesis. Graphical Abstract |
| first_indexed | 2024-03-07T14:42:35Z |
| format | Article |
| id | doaj.art-4b6d9efd2152429abadfde2ef5778fbc |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-07T14:42:35Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-4b6d9efd2152429abadfde2ef5778fbc2024-03-05T20:10:12ZengBMCJournal of Nanobiotechnology1477-31552024-02-0122112310.1186/s12951-024-02304-yMesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1Anna Łabędź-Masłowska0Luisa Vergori1Sylwia Kędracka-Krok2Elżbieta Karnas3Sylwia Bobis-Wozowicz4Małgorzata Sekuła-Stryjewska5Michał Sarna6Ramaroson Andriantsitohaina7Ewa K. Zuba-Surma8Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityINSERM U1063, Oxidative Stress and Metabolic Pathologies, Angers UniversityDepartment of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityLaboratory of Stem Cell Biotechnology, Malopolska Centre of Biotechnology, Jagiellonian UniversityDepartment of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityPhyMedExp, INSERM U1046, UMR CNRS 9214, Université de MontpellierDepartment of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityAbstract Mesenchymal stem cells/stromal cells (MSCs)-derived extracellular vesicles (EVs) mediate pro-regenerative effects in damaged ischemic tissues by regulating angiogenesis. MSCs-EVs modulate functions of cells including endogenous mature cells, progenitors and stem cells, resulting in restoration of blood flow. However, the mechanisms underlying such MSC-EV activity still remain poorly understood. The present study analyzes biological effects of bone marrow (BM) MSC-EVs on endothelial cells (ECs) in ischemic tissues both in in vitro and in vivo conditions and elucidates the molecular mechanisms underlying the tissue repair. MSC-EVs were isolated from murine BM-derived MSCs and their morphological, antigenic and molecular composition regarding protein and microRNA levels were evaluated to examine their properties. Global proteomic analysis demonstrated the presence in MSC-EVs of proteins regulating pro-regenerative pathways, including integrin α5 (Itgα5) and neuropilin-1 (NRP1) involved in lymphangiogenesis. MSC-EVs were also enriched in microRNAs regulating angiogenesis, TGF-β signaling and processes guiding cellular adhesion and interactions with extracellular matrix. The functional effects of MSC-EVs on capillary ECs in vitro included the increase of capillary-like tube formation and cytoprotection under normal and inflammatory conditions by inhibiting apoptosis. Notably, MSC-EVs enhanced also capillary-like tube formation of lymphatic ECs, which may be regulated by Itgα5 and NRP1. Moreover, in a mouse model of critical hind limb ischemia, MSC-EVs increased the recovery of blood flow in ischemic muscle tissue, which was accompanied with increased vascular density in vivo. This pro-angiogenic effect was associated with an increase in nitric oxide (NO) production via endothelial NO-synthase activation in ischemic muscles. Interestingly, MSC-EVs enhanced lymphangiogenesis, which has never been reported before. The study provides evidence on pro-angiogenic and novel pro-lymphangiogenic role of MSC-EVs on ECs in ischemic tissue mediated by their protein and miRNA molecular cargos. The results highlight Itgα5 and NRP1 carried by MSC-EVs as potential therapeutic targets to boost lymphangiogenesis. Graphical Abstracthttps://doi.org/10.1186/s12951-024-02304-yExtracellular vesiclesMesenchymal stem cellsIschemic tissue regenerationAngiogenesisLymphangiogenesis |
| spellingShingle | Anna Łabędź-Masłowska Luisa Vergori Sylwia Kędracka-Krok Elżbieta Karnas Sylwia Bobis-Wozowicz Małgorzata Sekuła-Stryjewska Michał Sarna Ramaroson Andriantsitohaina Ewa K. Zuba-Surma Mesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1 Journal of Nanobiotechnology Extracellular vesicles Mesenchymal stem cells Ischemic tissue regeneration Angiogenesis Lymphangiogenesis |
| title | Mesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1 |
| title_full | Mesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1 |
| title_fullStr | Mesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1 |
| title_full_unstemmed | Mesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1 |
| title_short | Mesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1 |
| title_sort | mesenchymal stem cell derived extracellular vesicles exert pro angiogenic and pro lymphangiogenic effects in ischemic tissues by transferring various micrornas and proteins including itga5 and nrp1 |
| topic | Extracellular vesicles Mesenchymal stem cells Ischemic tissue regeneration Angiogenesis Lymphangiogenesis |
| url | https://doi.org/10.1186/s12951-024-02304-y |
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