iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome

被引：75

作者：

Atchison, Leigh ^{[1
]}

Abutaleb, Nadia O. ^{[1
]}

Snyder-Mounts, Elizabeth ^{[1
]}

Gete, Yantenew ^{[2
]}

Ladha, Alim ^{[1
]}

Ribar, Thomas ^{[3
]}

Cao, Kan ^{[2
]}

Truskey, George A. ^{[1
]}

机构：

[1] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA

[2] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA

[3] Duke Univ, Duke iPSC Shared Resource Facil, Durham, NC USA

来源：

STEM CELL REPORTS | 2020年 / 14卷 / 02期

关键词：

PROGENITORS;

D O I：

10.1016/j.stemcr.2020.01.005

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：325 / 337

页数：13

共 23 条

[1] A Tissue Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome Using Human iPSC-derived Smooth Muscle Cells [J].