Abstract 384: Adult Mesenchymal Stem Cells from Patients with Ischemic Heart Disease Differentiate into a Vascular Phenotype and Improve Left Ventricular Function After Acute Myocardial Infarction in NOD/scid Mice: A 9.4T MRI Study
Purpose: Most human stem cell studies have been performed using unfractionated mononuclear bone marrow cells. However, little is known about the in vivo behaviour of isolated human mesenchymal stem cells (hMSCs). We investigated whether hMSCs from patients with ischemic heart disease engraft in the ischemic myocardium and improve left ventricular function in an immune-compromised mouse myocardial infarction model.
Methods: hMSCs were isolated from leftover bone marrow from patients with IHD who were enrolled in our clinical stem cell therapy trials. Myocardial infarction was induced in immune-compromised NOD/scid mice. After 10–20 minutes, hMSCs labelled with eGFP (2.0 × 10^5 cells in 20μl, n=12) or vehicle only (control group, n=13) were injected into the infarcted area. Sham operated mice were used as baseline (n=10). Two and 14 days after surgery, cardiac anatomy and function were serially assessed using a vertical 9.4T animal MRI. At day two, infarct size was determined by Gadolinium-DTPA delayed enhancement. Mice were subsequently sacrificed and presence and differentiation of engrafted cells was assessed.
Results: At day 2, infarct size as assessed by delayed enhancement MRI was similar in both groups (control 36±2% of LV mass vs. hMSC 33±2%, P=n.s.). Both groups showed a marked decrease in EF after 2 days (31±8 % vs. 33±9%, P=n.s.) as compared to baseline (51±3%, P<0.001). At day 14 EF deteriorated further in the control group (16 ± 6%). In contrast, hMSC treatment reduced further deterioration of EF, with an EF of 24±9% (P=0.017). There was a trend towards reduced LV volumes in the hMSC treated group (p=0.3). At histological examination eGFP labelled hMSCs were present in significant numbers both in the infarcted border zone and the free wall.The engrafted hMSCs stained positive for endothelial (von Willebrand-factor) and smooth muscle cell (α-smooth muscle actin) markers but not for cardiomyocyte markers.
Conclusions: Adult hMSCs from patients with IHD engraft in infarcted mouse myocardium and acquire a vascular phenotype, resulting in improved LV function. These results suggest that also hMSCs from patients with ischemic heart disease are an attractive cell type in clinical autologous cell-based therapy for the treatment of IHD.