Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction.
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.
Grauss
Robert W
RW
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Winter
Elizabeth M
EM
van Tuyn
John
J
Pijnappels
Daniël A
DA
Steijn
Rebecca Vicente
RV
Hogers
Bianca
B
van der Geest
Rob J
RJ
de Vries
Antoine A F
AA
Steendijk
Paul
P
van der Laarse
Arnoud
A
Gittenberger-de Groot
Adriana C
AC
Schalij
Martin J
MJ
Atsma
Douwe E
DE
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
C485184:enhanced green fluorescent protein; D014841:von Willebrand Factor; D049452:Green Fluorescent Proteins