Tissue-Engineered Vascular Grafts with Advanced Mechanical Strength from Human iPSCs

Cell Stem Cell. 2020 Feb 6;26(2):251-261.e8. doi: 10.1016/j.stem.2019.12.012. Epub 2020 Jan 16.

Abstract

Vascular smooth muscle cells (VSMCs) can be derived in large numbers from human induced pluripotent stem cells (hiPSCs) for producing tissue-engineered vascular grafts (TEVGs). However, hiPSC-derived TEVGs are hampered by low mechanical strength and significant radial dilation after implantation. Here, we report generation of hiPSC-derived TEVGs with mechanical strength comparable to native vessels used in arterial bypass grafts by utilizing biodegradable scaffolds, incremental pulsatile stretching, and optimal culture conditions. Following implantation into a rat aortic model, hiPSC-derived TEVGs show excellent patency without luminal dilation and effectively maintain mechanical and contractile function. This study provides a foundation for future production of non-immunogenic, cellularized hiPSC-derived TEVGs composed of allogenic vascular cells, potentially serving needs to a considerable number of patients whose dysfunctional vascular cells preclude TEVG generation via other methods.

Keywords: human induced pluripotent stem cells; tissue engineered vascular grafts; vascular smooth muscle cells.

Publication types

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

MeSH terms

  • Blood Vessel Prosthesis*
  • Humans
  • Induced Pluripotent Stem Cells*
  • Myocytes, Smooth Muscle
  • Tissue Engineering