Echocardiographic Evaluation of the Effects of Stem Cell Therapy on Perfusion and Function in Ischemic Cardiomyopathy

Abstract

BACKGROUND Small animal models of ischemic left ventricular (LV) dysfunction are important for the pre-clinical optimization of stem cell therapy. We hypothesized that temporal changes in LV function and regional perfusion after cell therapy can be assessed in mice using echocardiographic imaging. METHODS Wild-type mice (n=25) were studied 7 and 28 days after permanent ligation of the left anterior descending artery. Animals were randomized to receive closed-chest ultrasound-guided intramyocardial delivery of saline (n=13) or 5×105 multipotential adult progenitor cells (MAPC) (n=12) at day 7. Left ventricular end-diastolic (LVEDV) and end-systolic (LVESV) volume, left ventricular ejection fraction (LVEF), and stroke volume were measured by high-frequency echocardiography. Multiplanar assessment of perfusion and defect area size were made by myocardial contrast echocardiography (MCE). RESULTS Between day 7 and 28, MAPC-treated animals had a 40–50% reduction in defect size (p<0.001) and a 20–30% increase in total perfusion (p<0.01). Perfusion did not change in non-treated controls. Both LVEDV and LVESV increased between day 7 and 28 in both groups, however LVESV increased to a lesser degree in MAPC-treated versus control mice (+4.2±7.9 vs +19.2±22.0 μL, p<0.05). LVEF increased in the MAPC-treated mice and decreased in control mice (+3.0±4.3 vs −5.6±5.9 %, p<0.01). There was a significant linear relation between the change in LVEF and the change in either defect area size or total perfusion. CONCLUSIONS High-frequency echocardiography and MCE in murine models of ischemic LV dysfunction can be used to assess the response to stem cell therapy and to characterize the relationship between spatial flow, ventricular function and ventricular remodeling.

Multiple Intravenous Injections of Valproic Acid‐Induced Mesenchymal Stem Cell from Human‐Induced Pluripotent Stem Cells Improved Cardiac Function in an Acute Myocardial Infarction Rat Model

“…The pathophysiological changes of ventricular remodeling can be divided into early and late phases after AMI onset. The early phase involves expansion of the infarct area, and late remodeling involves time-dependent dilatation, distortion of ventricular shape, and mural hypertrophy [ 41 ].…”

N‐acetylcysteine prevents oxidized low‐density lipoprotein‐induced reduction of MG53 and enhances MG53 protective effect on bone marrow stem cells

“…MAPCs were isolated from bone marrow, clonally purified and well‐characterized multipotent cells with differentiation potential into a variety of cell lineages including endothelial cells, smooth muscle cells, neurons, hepatocytes and cardiac myocytes . MAPCs promote angiogenesis and improve cardiac and limb function when injected into the peri‐infarct areas in ischaemic mice . These cells have extensive replication potential, are commercially available at clinical grade (Athersys Inc, Cleveland, Ohio) and are non‐immunogenic for alloreactive cytotoxic T lymphocyte induction, thus without potential adverse immune reactions .…”

“…24,25,29,30 MAPCs promote angiogenesis and improve cardiac and limb function when injected into the peri-infarct areas in ischaemic mice. [31][32][33][34][35][36][37][38][39][40] These cells have extensive replication potential, are commercially available at clinical grade (Athersys Inc, Cleveland, Ohio) and are non-immunogenic for alloreactive cytotoxic T lymphocyte induction, thus without potential adverse immune reactions. 41,42 MAPCs have been approved for clinical studies in human patients with multiple disease indications including neurological, cardiovascular and inflammatory and immune diseases in the United States and Europe.…”

A novel method for quantitative myocardial contrast echocardiography in mice

“…In the research setting, studies are typically performed on cohorts of identically treated animals, and the ability to detect differences between treatment groups (rather than characterize disease in a single subject) is desired. Important research applications for MCE in small animals include phenotyping animal models (26,27) and assessing response to experimental therapy (15,21). The spatial extent of myocardium at risk or infarcted can be used as a powerful and versatile end point in many studies.…”