iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome
Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder caused by a point mutation in the Lamin A gene that produces the protein progerin. Progerin toxicity leads to accelerated aging and death from cardiovascular disease. To elucidate the effects of progerin on endothelial cells, we...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-02-01
|
| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671120300266 |
| _version_ | 1811287148469420032 |
|---|---|
| author | Leigh Atchison Nadia O. Abutaleb Elizabeth Snyder-Mounts Yantenew Gete Alim Ladha Thomas Ribar Kan Cao George A. Truskey |
| author_facet | Leigh Atchison Nadia O. Abutaleb Elizabeth Snyder-Mounts Yantenew Gete Alim Ladha Thomas Ribar Kan Cao George A. Truskey |
| author_sort | Leigh Atchison |
| collection | DOAJ |
| description | Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder caused by a point mutation in the Lamin A gene that produces the protein progerin. Progerin toxicity leads to accelerated aging and death from cardiovascular disease. To elucidate the effects of progerin on endothelial cells, we prepared tissue-engineered blood vessels (viTEBVs) using induced pluripotent stem cell-derived smooth muscle cells (viSMCs) and endothelial cells (viECs) from HGPS patients. HGPS viECs aligned with flow but exhibited reduced flow-responsive gene expression and altered NOS3 levels. Relative to viTEBVs with healthy cells, HGPS viTEBVs showed reduced function and exhibited markers of cardiovascular disease associated with endothelium. HGPS viTEBVs exhibited a reduction in both vasoconstriction and vasodilation. Preparing viTEBVs with HGPS viECs and healthy viSMCs only reduced vasodilation. Furthermore, HGPS viECs produced VCAM1 and E-selectin protein in TEBVs with healthy or HGPS viSMCs. In summary, the viTEBV model has identified a role of the endothelium in HGPS. : Atchison and colleagues produced hiPSC-derived vascular smooth muscle cells and vascular endothelial cells from healthy and progeria patients. These cells were used to fabricate functional tissue-engineered blood vessels that express key features of the progeria cardiovascular phenotype. This work provides a novel platform to study progeria and other cardiovascular diseases using iPSC-derived cells in an in vitro platform. Keywords: Hutchinson-Gilford progeria syndrome, tissue-engineered blood vessel, microphysiological system, induced pluripotent stem cells, vascular endothelium, smooth muscle cells, shear stress |
| first_indexed | 2024-04-13T03:12:32Z |
| format | Article |
| id | doaj.art-e7d2f440db154cccadc0aede2fec305b |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-13T03:12:32Z |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-e7d2f440db154cccadc0aede2fec305b2022-12-22T03:05:00ZengElsevierStem Cell Reports2213-67112020-02-01142325337iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria SyndromeLeigh Atchison0Nadia O. Abutaleb1Elizabeth Snyder-Mounts2Yantenew Gete3Alim Ladha4Thomas Ribar5Kan Cao6George A. Truskey7Department of Biomedical Engineering, Duke University, Durham, NC, USADepartment of Biomedical Engineering, Duke University, Durham, NC, USADepartment of Biomedical Engineering, Duke University, Durham, NC, USADepartment of Cell Biology and Molecular Genetics at University of Maryland, College Park, MD, USADepartment of Biomedical Engineering, Duke University, Durham, NC, USADuke iPSC Shared Resource Facility at Duke University, Durham, NC, USADepartment of Cell Biology and Molecular Genetics at University of Maryland, College Park, MD, USADepartment of Biomedical Engineering, Duke University, Durham, NC, USA; Corresponding authorSummary: Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder caused by a point mutation in the Lamin A gene that produces the protein progerin. Progerin toxicity leads to accelerated aging and death from cardiovascular disease. To elucidate the effects of progerin on endothelial cells, we prepared tissue-engineered blood vessels (viTEBVs) using induced pluripotent stem cell-derived smooth muscle cells (viSMCs) and endothelial cells (viECs) from HGPS patients. HGPS viECs aligned with flow but exhibited reduced flow-responsive gene expression and altered NOS3 levels. Relative to viTEBVs with healthy cells, HGPS viTEBVs showed reduced function and exhibited markers of cardiovascular disease associated with endothelium. HGPS viTEBVs exhibited a reduction in both vasoconstriction and vasodilation. Preparing viTEBVs with HGPS viECs and healthy viSMCs only reduced vasodilation. Furthermore, HGPS viECs produced VCAM1 and E-selectin protein in TEBVs with healthy or HGPS viSMCs. In summary, the viTEBV model has identified a role of the endothelium in HGPS. : Atchison and colleagues produced hiPSC-derived vascular smooth muscle cells and vascular endothelial cells from healthy and progeria patients. These cells were used to fabricate functional tissue-engineered blood vessels that express key features of the progeria cardiovascular phenotype. This work provides a novel platform to study progeria and other cardiovascular diseases using iPSC-derived cells in an in vitro platform. Keywords: Hutchinson-Gilford progeria syndrome, tissue-engineered blood vessel, microphysiological system, induced pluripotent stem cells, vascular endothelium, smooth muscle cells, shear stresshttp://www.sciencedirect.com/science/article/pii/S2213671120300266 |
| spellingShingle | Leigh Atchison Nadia O. Abutaleb Elizabeth Snyder-Mounts Yantenew Gete Alim Ladha Thomas Ribar Kan Cao George A. Truskey iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome Stem Cell Reports |
| title | iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome |
| title_full | iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome |
| title_fullStr | iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome |
| title_full_unstemmed | iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome |
| title_short | iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome |
| title_sort | ipsc derived endothelial cells affect vascular function in a tissue engineered blood vessel model of hutchinson gilford progeria syndrome |
| url | http://www.sciencedirect.com/science/article/pii/S2213671120300266 |
| work_keys_str_mv | AT leighatchison ipscderivedendothelialcellsaffectvascularfunctioninatissueengineeredbloodvesselmodelofhutchinsongilfordprogeriasyndrome AT nadiaoabutaleb ipscderivedendothelialcellsaffectvascularfunctioninatissueengineeredbloodvesselmodelofhutchinsongilfordprogeriasyndrome AT elizabethsnydermounts ipscderivedendothelialcellsaffectvascularfunctioninatissueengineeredbloodvesselmodelofhutchinsongilfordprogeriasyndrome AT yantenewgete ipscderivedendothelialcellsaffectvascularfunctioninatissueengineeredbloodvesselmodelofhutchinsongilfordprogeriasyndrome AT alimladha ipscderivedendothelialcellsaffectvascularfunctioninatissueengineeredbloodvesselmodelofhutchinsongilfordprogeriasyndrome AT thomasribar ipscderivedendothelialcellsaffectvascularfunctioninatissueengineeredbloodvesselmodelofhutchinsongilfordprogeriasyndrome AT kancao ipscderivedendothelialcellsaffectvascularfunctioninatissueengineeredbloodvesselmodelofhutchinsongilfordprogeriasyndrome AT georgeatruskey ipscderivedendothelialcellsaffectvascularfunctioninatissueengineeredbloodvesselmodelofhutchinsongilfordprogeriasyndrome |