Skeletal myoblast sheet transplantation enhanced regional improvement of cardiac function

Skeletal myoblast sheet transplantation enhanced regional improvement of cardiac function Due to several complications involving left ventricular assist device use and insufficient donors for heart transplantation for advanced cardiac failure treatment, regenerative therapy has been extensively studied. Autologous skeletal myoblast sheet transplantation improved left ventricular ejection fraction and exercise tolerability in 70% of advanced ischaemic cardiomyopathy patients (Miyagawa et al. 2017, Journal of American Heart Association). Transplanted sheets secret various cytokines (e.g. hepatocyte growth factor and vascular endothelial growth factor), which induce angiogenesis, resulting in functional recovery. However, it is unknown whether these secreted cytokines, regionally or globally, affect cardiac performance. We performed quantitative evaluation of left ventricular wall motion in each region using a dedicated workstation (Ziostation2, ZIO, Japan) with 320-slice cardiac computed tomographic images in a 25-year-old woman with symptomatic ischaemic cardiomyopathy showing 20% ejection fraction despite full revascularization and medication. Five sheets (3 cm in diameter) consisting of 3 × 108 myoblasts/sheet were transplanted anterior to the lateral wall. Post-operative cardiac function, particularly anterior to the lateral wall, improved to 37% ejection fraction by the second year. The moving distance between diastolic and systolic phase is displayed with colour scale in images of 3D reconstruction (Panel A) and short-axis view of left ventricle (Panel B) (Supplementary data online, Videos S1–S8). We placed 20 volumes of interest (VOIs) on the left ventricular myocardium according to 20-segment model in vertical long-axis view (Panel C, left) and short-axis view (right) of LV. The top panels show six VOIs on basal myocardium, the second from the top shows six VOIs on mid myocardium, the third from the top shows six VOIs on mid-apical myocardium, and the bottom panels show two VOIs on apical myocardium. Then we calculated the moving distances of VOIs and 20 segments in bull's eye are coloured according to moving distance of each VOI from <1.9 (white) to ≥8.0 (green) mm (Panel D). The area framed by a red broken line represents the region in which skeletal myoblast sheet transplanted. The left, middle, and right panels display the bull's eye before the myoblast sheet transplantation, 1, and 2 years after the surgery, respectively. As a result, the moving distances of VOIs under the transplanted area increased remarkably, and those out of the transplanted area increased slightly after one year. This indicated that the myocardium with viability under the transplanted sheets greatly benefited from the paracrine effect, and that the sheets had a modest effect even on the myocardium remote from the transplant site. View largeDownload slide View largeDownload slide Supplementary data are available at European Heart Journal - Cardiovascular Imaging online. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal – Cardiovascular Imaging Oxford University Press

Skeletal myoblast sheet transplantation enhanced regional improvement of cardiac function

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Publisher
Oxford University Press
Copyright
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
ISSN
2047-2404
D.O.I.
10.1093/ehjci/jey064
Publisher site
See Article on Publisher Site

Abstract

Due to several complications involving left ventricular assist device use and insufficient donors for heart transplantation for advanced cardiac failure treatment, regenerative therapy has been extensively studied. Autologous skeletal myoblast sheet transplantation improved left ventricular ejection fraction and exercise tolerability in 70% of advanced ischaemic cardiomyopathy patients (Miyagawa et al. 2017, Journal of American Heart Association). Transplanted sheets secret various cytokines (e.g. hepatocyte growth factor and vascular endothelial growth factor), which induce angiogenesis, resulting in functional recovery. However, it is unknown whether these secreted cytokines, regionally or globally, affect cardiac performance. We performed quantitative evaluation of left ventricular wall motion in each region using a dedicated workstation (Ziostation2, ZIO, Japan) with 320-slice cardiac computed tomographic images in a 25-year-old woman with symptomatic ischaemic cardiomyopathy showing 20% ejection fraction despite full revascularization and medication. Five sheets (3 cm in diameter) consisting of 3 × 108 myoblasts/sheet were transplanted anterior to the lateral wall. Post-operative cardiac function, particularly anterior to the lateral wall, improved to 37% ejection fraction by the second year. The moving distance between diastolic and systolic phase is displayed with colour scale in images of 3D reconstruction (Panel A) and short-axis view of left ventricle (Panel B) (Supplementary data online, Videos S1–S8). We placed 20 volumes of interest (VOIs) on the left ventricular myocardium according to 20-segment model in vertical long-axis view (Panel C, left) and short-axis view (right) of LV. The top panels show six VOIs on basal myocardium, the second from the top shows six VOIs on mid myocardium, the third from the top shows six VOIs on mid-apical myocardium, and the bottom panels show two VOIs on apical myocardium. Then we calculated the moving distances of VOIs and 20 segments in bull's eye are coloured according to moving distance of each VOI from <1.9 (white) to ≥8.0 (green) mm (Panel D). The area framed by a red broken line represents the region in which skeletal myoblast sheet transplanted. The left, middle, and right panels display the bull's eye before the myoblast sheet transplantation, 1, and 2 years after the surgery, respectively. As a result, the moving distances of VOIs under the transplanted area increased remarkably, and those out of the transplanted area increased slightly after one year. This indicated that the myocardium with viability under the transplanted sheets greatly benefited from the paracrine effect, and that the sheets had a modest effect even on the myocardium remote from the transplant site. View largeDownload slide View largeDownload slide Supplementary data are available at European Heart Journal - Cardiovascular Imaging online. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

European Heart Journal – Cardiovascular ImagingOxford University Press

Published: Apr 17, 2018

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