Membrane Particles Derived From Adipose Tissue Mesenchymal Stromal Cells Improve Endothelial Cell Barrier Integrity
Proinflammatory stimuli lead to endothelial injury, which results in pathologies such as cardiovascular diseases, autoimmune diseases, and contributes to alloimmune responses after organ transplantation. Both mesenchymal stromal cells (MSC) and the extracellular vesicles (EV) released by them are wi...
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| Format: | Article |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.650522/full |
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| author | Ana Merino Marta Sablik Sander S. Korevaar Carmen López-Iglesias Maitane Ortiz-Virumbrales Carla C. Baan Eleuterio Lombardo Martin J. Hoogduijn |
| author_facet | Ana Merino Marta Sablik Sander S. Korevaar Carmen López-Iglesias Maitane Ortiz-Virumbrales Carla C. Baan Eleuterio Lombardo Martin J. Hoogduijn |
| author_sort | Ana Merino |
| collection | DOAJ |
| description | Proinflammatory stimuli lead to endothelial injury, which results in pathologies such as cardiovascular diseases, autoimmune diseases, and contributes to alloimmune responses after organ transplantation. Both mesenchymal stromal cells (MSC) and the extracellular vesicles (EV) released by them are widely studied as regenerative therapy for the endothelium. However, for therapeutic application, the manipulation of living MSC and large-scale production of EV are major challenges. Membrane particles (MP) generated from MSC may be an alternative to the use of whole MSC or EV. MP are nanovesicles artificially generated from the membranes of MSC and possess some of the therapeutic properties of MSC. In the present study we investigated whether MP conserve the beneficial MSC effects on endothelial cell repair processes under inflammatory conditions. MP were generated by hypotonic shock and extrusion of MSC membranes. The average size of MP was 120 nm, and they showed a spherical shape. The effects of two ratios of MP (50,000; 100,000 MP per target cell) on human umbilical vein endothelial cells (HUVEC) were tested in a model of inflammation induced by TNFα. Confocal microscopy and flow cytometry showed that within 24 hours >90% of HUVEC had taken up MP. Moreover, MP ended up in the lysosomes of the HUVEC. In a co-culture system of monocytes and TNFα activated HUVEC, MP did not affect monocyte adherence to HUVEC, but reduced the transmigration of monocytes across the endothelial layer from 138 ± 61 monocytes per microscopic field in TNFα activated HUVEC to 61 ± 45 monocytes. TNFα stimulation induced a 2-fold increase in the permeability of the HUVEC monolayer measured by the translocation of FITC-dextran to the lower compartment of a transwell system. At a dose of 1:100,000 MP significantly decreased endothelial permeability (1.5-fold) respect to TNFα Stimulated HUVEC. Finally, MP enhanced the angiogenic potential of HUVEC in an in vitro Matrigel assay by stimulating the formation of angiogenic structures, such as percentage of covered area, total tube length, total branching points, total loops. In conclusion, MP show regenerative effects on endothelial cells, opening a new avenue for treatment of vascular diseases where inflammatory processes damage the endothelium. |
| first_indexed | 2024-12-14T02:17:05Z |
| format | Article |
| id | doaj.art-6c529fdd1fda4069a5ef572daec04477 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T02:17:05Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-6c529fdd1fda4069a5ef572daec044772022-12-21T23:20:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.650522650522Membrane Particles Derived From Adipose Tissue Mesenchymal Stromal Cells Improve Endothelial Cell Barrier IntegrityAna Merino0Marta Sablik1Sander S. Korevaar2Carmen López-Iglesias3Maitane Ortiz-Virumbrales4Carla C. Baan5Eleuterio Lombardo6Martin J. Hoogduijn7Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, NetherlandsNephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, NetherlandsNephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, NetherlandsMicroscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute, FHML Maastricht University, Maastricht, NetherlandsTakeda Madrid, Cell Therapy Technology Center, Madrid, SpainNephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, NetherlandsTakeda Madrid, Cell Therapy Technology Center, Madrid, SpainNephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, NetherlandsProinflammatory stimuli lead to endothelial injury, which results in pathologies such as cardiovascular diseases, autoimmune diseases, and contributes to alloimmune responses after organ transplantation. Both mesenchymal stromal cells (MSC) and the extracellular vesicles (EV) released by them are widely studied as regenerative therapy for the endothelium. However, for therapeutic application, the manipulation of living MSC and large-scale production of EV are major challenges. Membrane particles (MP) generated from MSC may be an alternative to the use of whole MSC or EV. MP are nanovesicles artificially generated from the membranes of MSC and possess some of the therapeutic properties of MSC. In the present study we investigated whether MP conserve the beneficial MSC effects on endothelial cell repair processes under inflammatory conditions. MP were generated by hypotonic shock and extrusion of MSC membranes. The average size of MP was 120 nm, and they showed a spherical shape. The effects of two ratios of MP (50,000; 100,000 MP per target cell) on human umbilical vein endothelial cells (HUVEC) were tested in a model of inflammation induced by TNFα. Confocal microscopy and flow cytometry showed that within 24 hours >90% of HUVEC had taken up MP. Moreover, MP ended up in the lysosomes of the HUVEC. In a co-culture system of monocytes and TNFα activated HUVEC, MP did not affect monocyte adherence to HUVEC, but reduced the transmigration of monocytes across the endothelial layer from 138 ± 61 monocytes per microscopic field in TNFα activated HUVEC to 61 ± 45 monocytes. TNFα stimulation induced a 2-fold increase in the permeability of the HUVEC monolayer measured by the translocation of FITC-dextran to the lower compartment of a transwell system. At a dose of 1:100,000 MP significantly decreased endothelial permeability (1.5-fold) respect to TNFα Stimulated HUVEC. Finally, MP enhanced the angiogenic potential of HUVEC in an in vitro Matrigel assay by stimulating the formation of angiogenic structures, such as percentage of covered area, total tube length, total branching points, total loops. In conclusion, MP show regenerative effects on endothelial cells, opening a new avenue for treatment of vascular diseases where inflammatory processes damage the endothelium.https://www.frontiersin.org/articles/10.3389/fimmu.2021.650522/fullmembrane particlesnanovesiclesmesenchymal stromal cellsendothelial cellsregenerationimmune cell interaction |
| spellingShingle | Ana Merino Marta Sablik Sander S. Korevaar Carmen López-Iglesias Maitane Ortiz-Virumbrales Carla C. Baan Eleuterio Lombardo Martin J. Hoogduijn Membrane Particles Derived From Adipose Tissue Mesenchymal Stromal Cells Improve Endothelial Cell Barrier Integrity Frontiers in Immunology membrane particles nanovesicles mesenchymal stromal cells endothelial cells regeneration immune cell interaction |
| title | Membrane Particles Derived From Adipose Tissue Mesenchymal Stromal Cells Improve Endothelial Cell Barrier Integrity |
| title_full | Membrane Particles Derived From Adipose Tissue Mesenchymal Stromal Cells Improve Endothelial Cell Barrier Integrity |
| title_fullStr | Membrane Particles Derived From Adipose Tissue Mesenchymal Stromal Cells Improve Endothelial Cell Barrier Integrity |
| title_full_unstemmed | Membrane Particles Derived From Adipose Tissue Mesenchymal Stromal Cells Improve Endothelial Cell Barrier Integrity |
| title_short | Membrane Particles Derived From Adipose Tissue Mesenchymal Stromal Cells Improve Endothelial Cell Barrier Integrity |
| title_sort | membrane particles derived from adipose tissue mesenchymal stromal cells improve endothelial cell barrier integrity |
| topic | membrane particles nanovesicles mesenchymal stromal cells endothelial cells regeneration immune cell interaction |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.650522/full |
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