Open AccessCardiomyogenic differentiation‐independent improvement of cardiac function by human cardiomyocyte progenitor cell injection in ischaemic mouse hearts
Author(s) -
den Haan Melina C.,
Grauss Robert W.,
Smits Anke M.,
Winter Elizabeth M.,
van Tuyn John,
Pijnappels Daniël A.,
Steendijk Paul,
GittenbergerDe Groot Adriana C.,
van der Laarse Arnoud,
Fibbe Willem E.,
de Vries Antoine A. F.,
Schalij Martin J.,
Doevendans Pieter A.,
Goumans MarieJosé,
Atsma Douwe E.
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01468.x
Subject(s) - ejection fraction , paracrine signalling , progenitor cell , cardiac function curve , medicine , cardiology , myocardial infarction , ventricular remodeling , in vivo , myocyte , stem cell , heart failure , biology , microbiology and biotechnology , receptor
We previously showed that human cardiomyocyte progenitor cells (hCMPCs) injected after myocardial infarction (MI) had differentiated into cardiomyocytes in vivo 3 months after MI. Here, we investigated the short‐term (2 weeks) effects of hCMPCs on the infarcted mouse myocardium. MI was induced in immunocompromised (NOD/scid) mice, immediately followed by intramyocardial injection of hCMPCs labelled with enhanced green fluorescent protein (hCMPC group) or vehicle only (control group). Sham‐operated mice served as reference. Cardiac performance was measured 2 and 14 days after MI by magnetic resonance imaging at 9.4 T. Left ventricular (LV) pressure–volume measurements were performed at day 15 followed by extensive immunohistological analysis. Animals injected with hCMPCs demonstrated a higher LV ejection fraction, lower LV end‐systolic volume and smaller relaxation time constant than control animals 14 days after MI. hCMPCs engrafted in the infarcted myocardium, did not differentiate into cardiomyocytes, but increased vascular density and proliferation rate in the infarcted and border zone area of the hCMPC group. Injected hCMPCs engraft into murine infarcted myocardium where they improve LV systolic function and attenuate the ventricular remodelling process 2 weeks after MI. Since no cardiac differentiation of hCMPCs was evident after 2 weeks, the observed beneficial effects were most likely mediated by paracrine factors, targeting amongst others vascular homeostasis. These results demonstrate that hCMPCs can be applied to repair infarcted myocardium without the need to undergo differentiation into cardiomyocytes.