Modeling diabetic endothelial dysfunction with patient‐specific induced pluripotent stem cells
Abstract Diabetes is a known risk factor for various cardiovascular complications, mediated by endothelial dysfunction. Despite the high prevalence of this metabolic disorder, there is a lack of in vitro models that recapitulate the complexity of genetic and environmental factors associated with dia...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Bioengineering & Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/btm2.10592 |
| _version_ | 1797556831441125376 |
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| author | Rayyan Gorashi Nancy Rivera‐Bolanos Caitlyn Dang Cedric Chai Beatrix Kovacs Sara Alharbi Syeda Subia Ahmed Yogesh Goyal Guillermo Ameer Bin Jiang |
| author_facet | Rayyan Gorashi Nancy Rivera‐Bolanos Caitlyn Dang Cedric Chai Beatrix Kovacs Sara Alharbi Syeda Subia Ahmed Yogesh Goyal Guillermo Ameer Bin Jiang |
| author_sort | Rayyan Gorashi |
| collection | DOAJ |
| description | Abstract Diabetes is a known risk factor for various cardiovascular complications, mediated by endothelial dysfunction. Despite the high prevalence of this metabolic disorder, there is a lack of in vitro models that recapitulate the complexity of genetic and environmental factors associated with diabetic endothelial dysfunction. Here, we utilized human induced pluripotent stem cell (iPSC)‐derived endothelial cells (ECs) to develop in vitro models of diabetic endothelial dysfunction. We found that the diabetic phenotype was recapitulated in diabetic patient‐derived iPSC‐ECs, even in the absence of a diabetogenic environment. Subsequent exposure to culture conditions that mimic the diabetic clinical chemistry induced a diabetic phenotype in healthy iPSC‐ECs but did not affect the already dysfunctional diabetic iPSC‐ECs. RNA‐seq analysis revealed extensive transcriptome‐wide differences between cells derived from healthy individuals and diabetic patients. The in vitro disease models were used as a screening platform which identified angiotensin receptor blockers (ARBs) that improved endothelial function in vitro for each patient. In summary, we present in vitro models of diabetic endothelial dysfunction using iPSC technology, taking into account the complexity of genetic and environmental factors in the metabolic disorder. Our study provides novel insights into the pathophysiology of diabetic endothelial dysfunction and highlights the potential of iPSC‐based models for drug discovery and personalized medicine. |
| first_indexed | 2024-03-10T17:08:32Z |
| format | Article |
| id | doaj.art-290ef4e9c16a46d9bb3f45750fe17a52 |
| institution | Directory Open Access Journal |
| issn | 2380-6761 |
| language | English |
| last_indexed | 2024-03-10T17:08:32Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj.art-290ef4e9c16a46d9bb3f45750fe17a522023-11-20T10:44:12ZengWileyBioengineering & Translational Medicine2380-67612023-11-0186n/an/a10.1002/btm2.10592Modeling diabetic endothelial dysfunction with patient‐specific induced pluripotent stem cellsRayyan Gorashi0Nancy Rivera‐Bolanos1Caitlyn Dang2Cedric Chai3Beatrix Kovacs4Sara Alharbi5Syeda Subia Ahmed6Yogesh Goyal7Guillermo Ameer8Bin Jiang9Department of Biomedical Engineering Northwestern University Evanston and Chicago Illinois USADepartment of Biomedical Engineering Northwestern University Evanston and Chicago Illinois USADepartment of Surgery Feinberg School of Medicine, Northwestern University Chicago Illinois USADepartment of Cell and Developmental Biology Northwestern University Feinberg School of Medicine Chicago Illinois USADepartment of Surgery Feinberg School of Medicine, Northwestern University Chicago Illinois USADepartment of Surgery Feinberg School of Medicine, Northwestern University Chicago Illinois USADepartment of Cell and Developmental Biology Northwestern University Feinberg School of Medicine Chicago Illinois USADepartment of Cell and Developmental Biology Northwestern University Feinberg School of Medicine Chicago Illinois USADepartment of Biomedical Engineering Northwestern University Evanston and Chicago Illinois USADepartment of Biomedical Engineering Northwestern University Evanston and Chicago Illinois USAAbstract Diabetes is a known risk factor for various cardiovascular complications, mediated by endothelial dysfunction. Despite the high prevalence of this metabolic disorder, there is a lack of in vitro models that recapitulate the complexity of genetic and environmental factors associated with diabetic endothelial dysfunction. Here, we utilized human induced pluripotent stem cell (iPSC)‐derived endothelial cells (ECs) to develop in vitro models of diabetic endothelial dysfunction. We found that the diabetic phenotype was recapitulated in diabetic patient‐derived iPSC‐ECs, even in the absence of a diabetogenic environment. Subsequent exposure to culture conditions that mimic the diabetic clinical chemistry induced a diabetic phenotype in healthy iPSC‐ECs but did not affect the already dysfunctional diabetic iPSC‐ECs. RNA‐seq analysis revealed extensive transcriptome‐wide differences between cells derived from healthy individuals and diabetic patients. The in vitro disease models were used as a screening platform which identified angiotensin receptor blockers (ARBs) that improved endothelial function in vitro for each patient. In summary, we present in vitro models of diabetic endothelial dysfunction using iPSC technology, taking into account the complexity of genetic and environmental factors in the metabolic disorder. Our study provides novel insights into the pathophysiology of diabetic endothelial dysfunction and highlights the potential of iPSC‐based models for drug discovery and personalized medicine.https://doi.org/10.1002/btm2.10592cardiovascular diseasesdiabetes mellitusdisease modelingdrug screeningendothelial cellsinduced pluripotent stem cells |
| spellingShingle | Rayyan Gorashi Nancy Rivera‐Bolanos Caitlyn Dang Cedric Chai Beatrix Kovacs Sara Alharbi Syeda Subia Ahmed Yogesh Goyal Guillermo Ameer Bin Jiang Modeling diabetic endothelial dysfunction with patient‐specific induced pluripotent stem cells Bioengineering & Translational Medicine cardiovascular diseases diabetes mellitus disease modeling drug screening endothelial cells induced pluripotent stem cells |
| title | Modeling diabetic endothelial dysfunction with patient‐specific induced pluripotent stem cells |
| title_full | Modeling diabetic endothelial dysfunction with patient‐specific induced pluripotent stem cells |
| title_fullStr | Modeling diabetic endothelial dysfunction with patient‐specific induced pluripotent stem cells |
| title_full_unstemmed | Modeling diabetic endothelial dysfunction with patient‐specific induced pluripotent stem cells |
| title_short | Modeling diabetic endothelial dysfunction with patient‐specific induced pluripotent stem cells |
| title_sort | modeling diabetic endothelial dysfunction with patient specific induced pluripotent stem cells |
| topic | cardiovascular diseases diabetes mellitus disease modeling drug screening endothelial cells induced pluripotent stem cells |
| url | https://doi.org/10.1002/btm2.10592 |
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