Cover Page. The handle holds various files of this Leiden University dissertation

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1 Cover Page The handle holds various files of this Leiden University dissertation Author: Haan, Melina C. den Title: Cell therapy in ischemic heart disease models : role of inflammation, paracrine factors and hypercholesterolemia Issue Date:

2 Cell therapy in ischemic heart disease models: role of inflammation, paracrine factors and hypercholesterolemia

3 Colophon The studies described in this thesis were performed at the department of Cardiology of the Leiden University Medical Center, Leiden, The Netherlands. The research in this thesis forms part of the TeRM SmartMix Program of The Netherlands Ministry of Economic Affairs and the Netherlands Ministry of Education, Culture and Science. The financial contribution of Abbott Vascular Servier Nederland Farma B.V. Toshiba Medical Systems Nederland Pfizer B.V. Dr. F.E. Posthumus Meyjesfonds Alrijne Zorggroep is gratefully acknowledged. Cover and illustration design by Bas van Os Layout and printed by Off Page, Amsterdam, The Netherlands ISBN Copyright Melina C. den Haan, Leiden, The Netherlands. All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, without prior written permission of the author.

4 Cell therapy in ischemic heart disease models: role of inflammation, paracrine factors and hypercholesterolemia Proefschrift ter verkrijging van de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker, volgens besluit van het College voor Promoties te verdedigen op woensdag 23 maart 2016 klokke 15:00 uur door Melina Cynthia den Haan geboren te Rijnsburg in 1986

5 Promotores Prof. dr. D.E. Atsma Prof. dr. W.E. Fibbe Leden promotiecommissie Prof. dr. S.A.J. Chamuleau (Universitair Medisch Centrum Utrecht) Prof. dr. M.C. Harmsen (Universitair Medisch Centrum Groningen) Prof. dr. M.J. Schalij Prof. dr. A.J. van Zonneveld The financial contribution of the Dutch Heart Foundation (NHS) is gratefully acknowledged.

6 Everybody is a genius. But if you judge a fish by its ability to climb a tree, it will live its whole life believing that it is stupid. Attributed to Albert Einstein (Excerpt from The Rhythm of Life: Living Every day with Passion and Purpose by Matthew Kelly, 2004) Voor Mama Voor Martijn 5

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8 Table of contents Chapter 1 General introduction and outline of the thesis 9 Part I Chapter 2 Chapter 3 Chapter 4 Part II Chapter 5 Cardiac inflammation after myocardial infarction and the potential of mesenchymal stromal cells for cell-based therapy 23 Post-myocardial infarct inflammation and the potential role of cell therapy 25 Cardiovascular Drugs and Therapy 2015 Feb; 29(1): Myocardial infarction models in NOD/Scid mice for cell therapy research: permanent ischemia vs ischemia-reperfusion 55 Springerplus 2015 Jul 10; 4: 336. doi: /s y Discrepant results of experimental human mesenchymal stromal cell therapy after myocardial infarction: are animal models robust enough? 73 Submitted for publication Cardiomyocyte progenitor cells as source for cell-based therapy in the infarcted heart 97 Cardiomyogenic differentiation-independent improvement of cardiac function by human cardiomyocyte progenitor cell injection in ischemic mouse hearts 99 Journal of Cellular and Molecular Medicine 2012 Jul; 16(7): Part III Chapter 6 Effects of hypercholesterolemia after myocardial ischemia-reperfusion injury 129 Impaired cardiac function in hypercholesterolemic APOE*3-Leiden mice after myocardial ischemia-reperfusion injury despite reduced infarct size and inflammation 131 Submitted for publication Chapter 7 Summary, conclusions and future perspectives 151 Samenvatting, conclusies en toekomstperspectieven 157 List of publications 163 Dankwoord 165 Curriculum Vitae 167 7

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