Injection of Human Bone Marrow and Mononuclear Cell Extract into Infarcted Mouse Hearts Results in Functional Improvement

Background: We have previously shown that mouse whole bone marrow cell (BMC) extract results in improvement of cardiac function and decreases scar size in a mouse model of myocardial infarction (MI), in the absence of intact cells. It is not clear if thes

Mesenchymal Stem Cells Secrete Multiple Cytokines That Promote Angiogenesis and Have Contrasting Effects on Chemotaxis and Apoptosis

We have previously shown that mesenchymal stem cells (MSC) improve function upon integration in ischemic myocardium. We examined whether specific cytokines and growth factors produced by MSCs are able to affect angiogenesis, cellular migration and apoptosis. Conditioned media (CM) was prepared by culturing MSC for 48 hours. CM displayed significantly elevated levels of VEGF, Monocyte Chemoattractant Protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), MIP-1β and monokine induced by IFN-γ (MIG) compared to control media. MSC contained RNA for these factors as detected by RT-PCR. CM was able to induce angiogenesis in canine vascular endothelial cells. MCP-1 and MIP-1α increased cell migration of MSC while VEGF reduced it. H9c2 cells treated with CM under hypoxic conditions for 24 hours displayed a 16% reduction in caspase-3 activity compared to controls. PI 3-kinase γ inhibitor had no effect on controls but reversed the effect of CM on caspase-3 activity. MCP-1 alone mimicked the protective effect of CM while the PI 3-Kγ inhibitor did not reverse the effect of MCP-1. CM reduced phospho-BAD (Ser112) and phospho-Akt (Ser473) while increasing phospho-Akt (Thr308). MCP-1 reduced the level of phospho-Akt (Ser473) while having no effect on the other two; the PI 3-Kγ inhibitor did not alter the MCP-1 effect. ERK 1/2 phosphorylation was reduced in CM treated H9c2 cells, and inhibition of ERK 1/2 reduced the phosphorylation of Akt (Ser473), Akt (Thr308) and Bad (Ser112). In conclusion, MSC synthesize and secrete multiple paracrine factors that are able to affect MSC migration, promote angiogenesis and reduce apoptosis. While both MCP-1 and PI3-kinase are involved in the protective effect, they are independent of each other. It is likely that multiple pro-survival factors in addition to MCP-1 are secreted by MSC which act on divergent intracellular signaling pathways

Assessment of acute myocardial infarction: current status and recommendations from the North American society for cardiovascular imaging and the European society of cardiac radiology

There are a number of imaging tests that are used in the setting of acute myocardial infarction and acute coronary syndrome. Each has their strengths and limitations. Experts from the European Society of Cardiac Radiology and the North American Society for Cardiovascular Imaging together with other prominent imagers reviewed the literature. It is clear that there is a definite role for imaging in these patients. While comparative accuracy, convenience and cost have largely guided test decisions in the past, the introduction of newer tests is being held to a higher standard which compares patient outcomes. Multicenter randomized comparative effectiveness trials with outcome measures are required

Preclinical Studies of Stem Cell Therapy for Heart Disease

As part of the TACTICS (Transnational Alliance for Regenerative Therapies in Cardiovascular Syndromes) series to enhance regenerative medicine, here, we discuss the role of preclinical studies designed to advance stem cell therapies for cardiovascular disease. The quality of this research has improved over the past 10 to 15 years and overall indicates that cell therapy promotes cardiac repair. However, many issues remain, including inability to provide complete cardiac recovery. Recent studies question the need for intact cells suggesting that harnessing what the cells release is the solution. Our contribution describes important breakthroughs and current directions in a cell-based approach to alleviating cardiovascular disease