Atherogenic Cytokines Regulate VEGF-A-Induced Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Endothelial Cells
Coronary artery stenting or angioplasty procedures frequently result in long-term endothelial dysfunction or loss and complications including arterial thrombosis and myocardial infarction. Stem cell-based therapies have been proposed to support endothelial regeneration. Mesenchymal stem cells (MSCs)...
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| Language: | English |
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Wiley
2015-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2015/498328 |
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| author | Izuagie Attairu Ikhapoh Christopher J. Pelham Devendra K. Agrawal |
| author_facet | Izuagie Attairu Ikhapoh Christopher J. Pelham Devendra K. Agrawal |
| author_sort | Izuagie Attairu Ikhapoh |
| collection | DOAJ |
| description | Coronary artery stenting or angioplasty procedures frequently result in long-term endothelial dysfunction or loss and complications including arterial thrombosis and myocardial infarction. Stem cell-based therapies have been proposed to support endothelial regeneration. Mesenchymal stem cells (MSCs) differentiate into endothelial cells (ECs) in the presence of VEGF-A in vitro. Application of VEGF-A and MSC-derived ECs at the interventional site is a complex clinical challenge. In this study, we examined the effect of atherogenic cytokines (IL-6, TNFα, and Ang II) on EC differentiation and function. MSCs (CD44+, CD73+, CD90+, CD14−, and CD45−) were isolated from the bone marrow of Yucatan microswine. Naïve MSCs cultured in differentiation media containing VEGF-A (50 ng/mL) demonstrated increased expression of EC-specific markers (vWF, PECAM-1, and VE-cadherin), VEGFR-2 and Sox18, and enhanced endothelial tube formation. IL-6 or TNFα caused a dose-dependent attenuation of EC marker expression in VEGF-A-stimulated MSCs. In contrast, Ang II enhanced EC marker expression in VEGF-A-stimulated MSCs. Addition of Ang II to VEGF-A and IL-6 or TNFα was sufficient to rescue the EC phenotype. Thus, Ang II promotes but IL-6 and TNFα inhibit VEGF-A-induced differentiation of MSCs into ECs. These findings have important clinical implications for therapies intended to increase cardiac vascularity and reendothelialize coronary arteries following intervention. |
| format | Article |
| id | doaj-art-18e125ce8cf64c168d4fd8266534c2f1 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
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| series | Stem Cells International |
| spelling | doaj-art-18e125ce8cf64c168d4fd8266534c2f12025-02-03T01:02:06ZengWileyStem Cells International1687-966X1687-96782015-01-01201510.1155/2015/498328498328Atherogenic Cytokines Regulate VEGF-A-Induced Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Endothelial CellsIzuagie Attairu Ikhapoh0Christopher J. Pelham1Devendra K. Agrawal2Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USADepartment of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USADepartment of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USACoronary artery stenting or angioplasty procedures frequently result in long-term endothelial dysfunction or loss and complications including arterial thrombosis and myocardial infarction. Stem cell-based therapies have been proposed to support endothelial regeneration. Mesenchymal stem cells (MSCs) differentiate into endothelial cells (ECs) in the presence of VEGF-A in vitro. Application of VEGF-A and MSC-derived ECs at the interventional site is a complex clinical challenge. In this study, we examined the effect of atherogenic cytokines (IL-6, TNFα, and Ang II) on EC differentiation and function. MSCs (CD44+, CD73+, CD90+, CD14−, and CD45−) were isolated from the bone marrow of Yucatan microswine. Naïve MSCs cultured in differentiation media containing VEGF-A (50 ng/mL) demonstrated increased expression of EC-specific markers (vWF, PECAM-1, and VE-cadherin), VEGFR-2 and Sox18, and enhanced endothelial tube formation. IL-6 or TNFα caused a dose-dependent attenuation of EC marker expression in VEGF-A-stimulated MSCs. In contrast, Ang II enhanced EC marker expression in VEGF-A-stimulated MSCs. Addition of Ang II to VEGF-A and IL-6 or TNFα was sufficient to rescue the EC phenotype. Thus, Ang II promotes but IL-6 and TNFα inhibit VEGF-A-induced differentiation of MSCs into ECs. These findings have important clinical implications for therapies intended to increase cardiac vascularity and reendothelialize coronary arteries following intervention.http://dx.doi.org/10.1155/2015/498328 |
| spellingShingle | Izuagie Attairu Ikhapoh Christopher J. Pelham Devendra K. Agrawal Atherogenic Cytokines Regulate VEGF-A-Induced Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Endothelial Cells Stem Cells International |
| title | Atherogenic Cytokines Regulate VEGF-A-Induced Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Endothelial Cells |
| title_full | Atherogenic Cytokines Regulate VEGF-A-Induced Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Endothelial Cells |
| title_fullStr | Atherogenic Cytokines Regulate VEGF-A-Induced Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Endothelial Cells |
| title_full_unstemmed | Atherogenic Cytokines Regulate VEGF-A-Induced Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Endothelial Cells |
| title_short | Atherogenic Cytokines Regulate VEGF-A-Induced Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Endothelial Cells |
| title_sort | atherogenic cytokines regulate vegf a induced differentiation of bone marrow derived mesenchymal stem cells into endothelial cells |
| url | http://dx.doi.org/10.1155/2015/498328 |
| work_keys_str_mv | AT izuagieattairuikhapoh atherogeniccytokinesregulatevegfainduceddifferentiationofbonemarrowderivedmesenchymalstemcellsintoendothelialcells AT christopherjpelham atherogeniccytokinesregulatevegfainduceddifferentiationofbonemarrowderivedmesenchymalstemcellsintoendothelialcells AT devendrakagrawal atherogeniccytokinesregulatevegfainduceddifferentiationofbonemarrowderivedmesenchymalstemcellsintoendothelialcells |