A cardiac patch from aligned microvessel and cardiomyocyte patches.

A cardiac patch from aligned microvessel and cardiomyocyte patches.
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DOI:
10.1002/term.2568
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发表时间:
2018-03
影响因子:
3.3
通讯作者:
Tranquillo RT
Tranquillo RT
中科院分区:
工程技术3区
文献类型:
--
作者:
Schaefer JA;Guzman PA;Riemenschneider SB;Kamp TJ;Tranquillo RT

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Cardiac tissue engineering aims to produce replacement tissue patches in the lab to replace or treat infarcted myocardium. However, current patches lack pre-formed microvascularization and are therefore limited in thickness and force production. In the present study, we sought to assess whether a bi-layer patch composed of a layer made from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a microvessel layer composed of self-assembled human blood outgrowth endothelial cells (BOECs) and pericytes (PCs) was capable of engrafting on the epicardial surface of a nude rat infarct model and becoming perfused by the host four weeks after acute implantation. The bi-layer configuration was found to increase the twitch force production, improve hiPSC-CM survival and maturation, and increase patent microvessel lumens compared to time-matched single layer controls after two weeks of in vitro culture. Upon implantation, the patch microvessels sprouted into the CM layer of the patch and inosculated with the host vasculature as evidenced by species-specific perfusion labels and erythrocyte staining. Our results demonstrate the added microvessel layer of a bi-layer patch substantially improves in vitro functionality, and the bi-layer patch is capable of engraftment with rapid microvessel inosculation on injured myocardium. The bi-layer format will allow for scaling up in size through the addition of layers to obtain thicker tissues generating greater force in the future.
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