Molecular and environmental cues in cardiac differentiation of mesenchymal stem cells

Leiden Repository

Molecular and environmental cues in cardiac differentiation of mesenchymal stem cells

Title: Molecular and environmental cues in cardiac differentiation of mesenchymal stem cells
Author: Ramkisoensing, Arti Anushka
Publisher: Department Cardiology, Faculty of Medicine / Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2014-05-07
Keywords: Connexin 43
Mesenchymal stem cells
Cardiac differentiation
Stem cell therapy
Abstract: In this thesis molecular and environmental cues in cardiac differentiation of mesenchymal stem cells were investigated. The main conclusions were that the cardiac differentiation potential of human mesenchymal stem cells negatively correlates with donor age. This in its own shows a negative relationship with connexin 43 levels in these cells. However, a causal relationship between connexin 43 expression levels and cardiomyogenic differentiation potential only exists for human mesenchymal stem cells from prenatal sources, i.e. while knockdown of connexin 43 expression in fetal human mesenchymal stem cells inhibits their ability to differentiate into cardiomyocytes, connexin 43 overexpression in adult human mesenchymal stem cells does not endow them with cardiomyogenic differentiation capacity. In addition, co-culture studies showed that the alignment and distribution of mesenchymal stem cells affect their electrical integration into host myocardium and are major determinants of their pro-arrhythmic risk. The mechanisms underlying the pro-arrhythmic effects of hMSCs are to some extent comparable to those of cardiac myofibroblasts, cells that are found in fibrotic myocardium
Description: Promotores: M.J. Schalij, D.E. Atsma Co-promotor: A.A.F. de Vries
With summary in Dutch
Faculty: LUMC
Citation: Ramkisoensing, A.A., 2014, Doctoral thesis, Leiden University
ISBN: 9789461086679
Handle: http://hdl.handle.net/1887/25711
 

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