Leiden University Scholarly Publications

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Haan, Melina Cynthia den (2016)

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

Doctoral Thesis
This thesis focuses on the potential of cell-based therapy in ischemic heart disease and the role of the inflammatory response after myocardial infarction (MI). Chapter 2 reviews the specific myocardial inflammatory events that occur following MI and explores the potential role of cell therapy, in specific of the mesenchymal stromal cell (MSC), to positively influence this process. In chapter 3 we studied the usefulness of a clinically relevant transient ischemia MI model in immunodeficient mice to investigate the potential of human stem cell therapy and compared this to the commonly used animal MI model via permanent ischemia. Next, in chapter 4 we aimed to extend our previous research regarding the positive therapeutic effects of MSC therapy after MI by injecting MSCs stimulated with the pro-inflammatory cytokine interferon-γ, since pro-inflammatory priming has shown additional beneficial effects in several experimental disease models. Chapter 5 evaluates the short-term effect...Show moreThis thesis focuses on the potential of cell-based therapy in ischemic heart disease and the role of the inflammatory response after myocardial infarction (MI). Chapter 2 reviews the specific myocardial inflammatory events that occur following MI and explores the potential role of cell therapy, in specific of the mesenchymal stromal cell (MSC), to positively influence this process. In chapter 3 we studied the usefulness of a clinically relevant transient ischemia MI model in immunodeficient mice to investigate the potential of human stem cell therapy and compared this to the commonly used animal MI model via permanent ischemia. Next, in chapter 4 we aimed to extend our previous research regarding the positive therapeutic effects of MSC therapy after MI by injecting MSCs stimulated with the pro-inflammatory cytokine interferon-γ, since pro-inflammatory priming has shown additional beneficial effects in several experimental disease models. Chapter 5 evaluates the short-term effect of human cardiomyocyte progenitor cell infusion on cardiac function in an animal MI model. Chapter 6 discusses the effect of diet-induced hypercholesterolemia on both cardiac function and inflammation after myocardial ischemia-reperfusion injury. Finally, chapter 7 provides an overview of the results described in this thesis, and discusses future perspectives.Show less
Cardiac function
Hypercholesterolemia
Inflammation
Stem cell
Ischemia-reperfusion
Myocardial infarction
All authors
Haan, Melina Cynthia den
Supervisor
Atsma, D.E.; Fibbe, W.E.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2016-03-23
ISBN (print)
9789461826558

Funding

Sponsorship
TeRM Smartmix Program Abbott Vascular Servier Nederland Farma B.V. Toshiba Medical Systems Nederland Pfizer B.V. Dr. F.E. Posthumus Meyjesfonds Alrijne Zorggroep Nederlandse Hartstichting