Title | iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | L Atchison, NO Abutaleb, E Snyder-Mounts, Y Gete, A Ladha, T Ribar, K Cao, and GA Truskey |
Journal | Stem Cell Reports |
Volume | 14 |
Issue | 2 |
Start Page | 325 |
Pagination | 325 - 337 |
Date Published | 02/2020 |
Abstract | 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. |
DOI | 10.1016/j.stemcr.2020.01.005 |
Short Title | Stem Cell Reports |