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

Stem Cell Reports. 2020 Feb 11;14(2):325-337. doi: 10.1016/j.stemcr.2020.01.005. Epub 2020 Feb 6.


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.

Keywords: Hutchinson-Gilford progeria syndrome; induced pluripotent stem cells; microphysiological system; shear stress; smooth muscle cells; tissue-engineered blood vessel; vascular endothelium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Blood Vessel Prosthesis*
  • Blood Vessels / pathology
  • Blood Vessels / physiopathology*
  • Clone Cells
  • Gene Expression Regulation
  • Humans
  • Induced Pluripotent Stem Cells / pathology*
  • Male
  • Models, Biological*
  • Phenotype
  • Progeria / pathology*
  • Tissue Donors
  • Tissue Engineering*