title: Cardiomyogenic differentiation-independent improvement of cardiac function by human cardiomyocyte progenitor cell injection in ischaemic mouse hearts.
abstract: 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.
authors: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Melina C
authors: MC
authors: den Haan
authors: Robert W
authors: RW
authors: Grauss
authors: Anke M
authors: AM
authors: Smits
authors: Elizabeth M
authors: EM
authors: Winter
authors: John
authors: J
authors: van Tuyn
authors: Daniël A
authors: DA
authors: Pijnappels
authors: Paul
authors: P
authors: Steendijk
authors: Adriana C
authors: AC
authors: Gittenberger-De Groot
authors: Arnoud
authors: A
authors: van der Laarse
authors: Willem E
authors: WE
authors: Fibbe
authors: Antoine A F
authors: AA
authors: de Vries
authors: Martin J
authors: MJ
authors: Schalij
authors: Pieter A
authors: PA
authors: Doevendans
authors: Marie-José
authors: MJ
authors: Goumans
authors: Douwe E
authors: DE
authors: Atsma
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D032446:Myoblasts / Q000166:cytology / Q000637:transplantation*; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology*; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins