Diabetic state of human coronary artery endothelial cells results in altered effects of bone mesenchymal stem cell‐derived extracellular vesicles
Abstract Human bone mesenchymal stem cell‐derived extracellular vesicles (HBMSC‐EV) have been used successfully in animal models of myocardial ischemia, yet have dampened effects in metabolic syndrome through unknown mechanisms. This study demonstrates the basal differences between non‐diabetic huma...
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.15866 |
| _version_ | 1797375135960793088 |
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| author | Cynthia M. Xu Catherine Karbasiafshar Rayane Brinck‐Teixeira Mark Broadwin Frank W. Sellke M. Ruhul Abid |
| author_facet | Cynthia M. Xu Catherine Karbasiafshar Rayane Brinck‐Teixeira Mark Broadwin Frank W. Sellke M. Ruhul Abid |
| author_sort | Cynthia M. Xu |
| collection | DOAJ |
| description | Abstract Human bone mesenchymal stem cell‐derived extracellular vesicles (HBMSC‐EV) have been used successfully in animal models of myocardial ischemia, yet have dampened effects in metabolic syndrome through unknown mechanisms. This study demonstrates the basal differences between non‐diabetic human coronary artery endothelial cells (HCAEC) and diabetic HCAEC (DM‐HCAEC), and how these cells respond to the treatment of HBMSC‐EV. HCAEC and DM‐HCAEC were treated with HBMSC‐EV for 6 h. Proteomics, western blot analysis, and tube formation assays were performed. Key metabolic, growth, and stress/starvation cellular responses were significantly altered in DM‐HCAEC in comparison to that of HCAEC at baseline. Proteomics demonstrated increased phosphorus metabolic process and immune pathways and decreased RNA processing and biosynthetic pathways in DM‐HCAEC. Similar to previous in vivo findings, HCAEC responded to the HBMSC‐EV with regenerative and anti‐inflammatory effects through the upregulation of multiple RNA pathways and downregulation of immune cell activation pathways. In contrast, DM‐HCAEC had a significantly diminished response to HBMSC‐EV, likely due to the baseline abnormalities in DM‐HCAEC. To achieve the full benefits of HBMSC‐EV and for a successful transition of this potential therapeutic agent to clinical studies, the abnormalities found in DM‐HCAEC will need to be further studied. |
| first_indexed | 2024-03-08T19:17:50Z |
| format | Article |
| id | doaj.art-b2931ec8e60a4b42b95b2ed60482ae08 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-08T19:17:50Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-b2931ec8e60a4b42b95b2ed60482ae082023-12-27T03:58:32ZengWileyPhysiological Reports2051-817X2023-12-011124n/an/a10.14814/phy2.15866Diabetic state of human coronary artery endothelial cells results in altered effects of bone mesenchymal stem cell‐derived extracellular vesiclesCynthia M. Xu0Catherine Karbasiafshar1Rayane Brinck‐Teixeira2Mark Broadwin3Frank W. Sellke4M. Ruhul Abid5Cardiovascular Research Center, Rhode Island Hospital Providence Rhode Island USACardiovascular Research Center, Rhode Island Hospital Providence Rhode Island USACardiovascular Research Center, Rhode Island Hospital Providence Rhode Island USACardiovascular Research Center, Rhode Island Hospital Providence Rhode Island USACardiovascular Research Center, Rhode Island Hospital Providence Rhode Island USACardiovascular Research Center, Rhode Island Hospital Providence Rhode Island USAAbstract Human bone mesenchymal stem cell‐derived extracellular vesicles (HBMSC‐EV) have been used successfully in animal models of myocardial ischemia, yet have dampened effects in metabolic syndrome through unknown mechanisms. This study demonstrates the basal differences between non‐diabetic human coronary artery endothelial cells (HCAEC) and diabetic HCAEC (DM‐HCAEC), and how these cells respond to the treatment of HBMSC‐EV. HCAEC and DM‐HCAEC were treated with HBMSC‐EV for 6 h. Proteomics, western blot analysis, and tube formation assays were performed. Key metabolic, growth, and stress/starvation cellular responses were significantly altered in DM‐HCAEC in comparison to that of HCAEC at baseline. Proteomics demonstrated increased phosphorus metabolic process and immune pathways and decreased RNA processing and biosynthetic pathways in DM‐HCAEC. Similar to previous in vivo findings, HCAEC responded to the HBMSC‐EV with regenerative and anti‐inflammatory effects through the upregulation of multiple RNA pathways and downregulation of immune cell activation pathways. In contrast, DM‐HCAEC had a significantly diminished response to HBMSC‐EV, likely due to the baseline abnormalities in DM‐HCAEC. To achieve the full benefits of HBMSC‐EV and for a successful transition of this potential therapeutic agent to clinical studies, the abnormalities found in DM‐HCAEC will need to be further studied.https://doi.org/10.14814/phy2.15866diabeteshuman bone mesenchymal stem cell‐derived extracellular vesicleshuman coronary artery endothelial cellsmetabolic syndrome |
| spellingShingle | Cynthia M. Xu Catherine Karbasiafshar Rayane Brinck‐Teixeira Mark Broadwin Frank W. Sellke M. Ruhul Abid Diabetic state of human coronary artery endothelial cells results in altered effects of bone mesenchymal stem cell‐derived extracellular vesicles Physiological Reports diabetes human bone mesenchymal stem cell‐derived extracellular vesicles human coronary artery endothelial cells metabolic syndrome |
| title | Diabetic state of human coronary artery endothelial cells results in altered effects of bone mesenchymal stem cell‐derived extracellular vesicles |
| title_full | Diabetic state of human coronary artery endothelial cells results in altered effects of bone mesenchymal stem cell‐derived extracellular vesicles |
| title_fullStr | Diabetic state of human coronary artery endothelial cells results in altered effects of bone mesenchymal stem cell‐derived extracellular vesicles |
| title_full_unstemmed | Diabetic state of human coronary artery endothelial cells results in altered effects of bone mesenchymal stem cell‐derived extracellular vesicles |
| title_short | Diabetic state of human coronary artery endothelial cells results in altered effects of bone mesenchymal stem cell‐derived extracellular vesicles |
| title_sort | diabetic state of human coronary artery endothelial cells results in altered effects of bone mesenchymal stem cell derived extracellular vesicles |
| topic | diabetes human bone mesenchymal stem cell‐derived extracellular vesicles human coronary artery endothelial cells metabolic syndrome |
| url | https://doi.org/10.14814/phy2.15866 |
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