title: Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction.
abstract: Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immune-compromised mouse AMI model was studied. Enhanced green fluorescent protein-labeled hMSCs from IHD patients (hMSC group: 2 x 10(5) cells in 20 microl, n = 12) or vehicle only (medium group: n = 14) were injected into infarcted myocardium of NOD/scid mice. Sham-operated mice were used as the control (n = 10). Cardiac anatomy and function were serially assessed using 9.4-T magnetic resonance imaging (MRI); 2 wk after cell transplantation, immunohistological analysis was performed. At day 2, delayed-enhancement MRI showed no difference in myocardial infarction (MI) size between the hMSC and medium groups (33 +/- 2% vs. 36 +/- 2%; P = not significant). A comparable increase in left ventricular (LV) volume and decrease in ejection fraction (EF) was observed in both MI groups. However, at day 14, EF was higher in the hMSC than in the medium group (24 +/- 3% vs. 16 +/- 2%; P < 0.05). This was accompanied by increased vascularity and reduced thinning of the infarct scar. Engrafted hMSCs (4.1 +/- 0.3% of injected cells) expressed von Willebrand factor (16.9 +/- 2.7%) but no stringent cardiac or smooth muscle markers. hMSCs from patients with IHD engraft in infarcted mouse myocardium and preserve LV function 2 wk after AMI, potentially through an enhancement of scar vascularity and a reduction of wall thinning.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grauss
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Winter
authors.forename: John
authors.initials: J
authors.lastname: van Tuyn
authors.forename: Daniël A
authors.initials: DA
authors.lastname: Pijnappels
authors.forename: Rebecca Vicente
authors.initials: RV
authors.lastname: Steijn
authors.forename: Bianca
authors.initials: B
authors.lastname: Hogers
authors.forename: Rob J
authors.initials: RJ
authors.lastname: van der Geest
authors.forename: Antoine A F
authors.initials: AA
authors.lastname: de Vries
authors.forename: Paul
authors.initials: P
authors.lastname: Steendijk
authors.forename: Arnoud
authors.initials: A
authors.lastname: van der Laarse
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schalij
authors.forename: Douwe E
authors.initials: DE
authors.lastname: Atsma
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001835:Body Weight; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000473:pathology; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D017202:Myocardial Ischemia / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009929:Organ Size; D012107:Research Design; D013318:Stroke Volume; D013997:Time Factors; D014161:Transduction, Genetic; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: C485184:enhanced green fluorescent protein; D014841:von Willebrand Factor; D049452:Green Fluorescent Proteins