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Nat Commun. 2019 Feb 4;10(1):584. doi: 10.1038/s41467-019-08388-7.

Patterned human microvascular grafts enable rapid vascularization and increase perfusion in infarcted rat hearts.

Redd MA1,2,3, Zeinstra N1,2,3, Qin W1, Wei W1, Martinson A2,3,4, Wang Y3,5, Wang RK1, Murry CE6,7,8,9,10, Zheng Y11,12,13.

Author information

1
Department of Bioengineering, University of Washington, Seattle, WA, 98109, USA.
2
Center for Cardiovascular Biology, University of Washington, Seattle, WA, 98109, USA.
3
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98109, USA.
4
Department of Pathology, University of Washington, Seattle, WA, 98109, USA.
5
Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA, 98109, USA.
6
Department of Bioengineering, University of Washington, Seattle, WA, 98109, USA. murry@uw.edu.
7
Center for Cardiovascular Biology, University of Washington, Seattle, WA, 98109, USA. murry@uw.edu.
8
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98109, USA. murry@uw.edu.
9
Department of Pathology, University of Washington, Seattle, WA, 98109, USA. murry@uw.edu.
10
Department of Medicine/Cardiology, University of Washington, Seattle, WA, 98109, USA. murry@uw.edu.
11
Department of Bioengineering, University of Washington, Seattle, WA, 98109, USA. yingzy@uw.edu.
12
Center for Cardiovascular Biology, University of Washington, Seattle, WA, 98109, USA. yingzy@uw.edu.
13
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98109, USA. yingzy@uw.edu.

Abstract

Vascularization and efficient perfusion are long-standing challenges in cardiac tissue engineering. Here we report engineered perfusable microvascular constructs, wherein human embryonic stem cell-derived endothelial cells (hESC-ECs) are seeded both into patterned microchannels and the surrounding collagen matrix. In vitro, the hESC-ECs lining the luminal walls readily sprout and anastomose with de novo-formed endothelial tubes in the matrix under flow. When implanted on infarcted rat hearts, the perfusable microvessel grafts integrate with coronary vasculature to a greater degree than non-perfusable self-assembled constructs at 5 days post-implantation. Optical microangiography imaging reveal that perfusable grafts have 6-fold greater vascular density, 2.5-fold higher vascular velocities and >20-fold higher volumetric perfusion rates. Implantation of perfusable grafts containing additional hESC-derived cardiomyocytes show higher cardiomyocyte and vascular density. Thus, pre-patterned vascular networks enhance vascular remodeling and accelerate coronary perfusion, potentially supporting cardiac tissues after implantation. These findings should facilitate the next generation of cardiac tissue engineering design.

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