Human Umbilical Cord Blood Mononuclear Cells for the Treatment of Acute Myocardial Infarction

Abstract

Cell transplantation is a new treatment to improve cardiac function in hearts that have been damaged by myocardial infarction. We have investigated the use of human umbilical cord blood mononuclear progenitor cells (HUCBC) for the treatment of acute myocardial infarction. The control group consisted of 24 normal rats with no interventions. The infarct + vehicle group consisted of 33 rats that underwent left anterior descending coronary artery (LAD) ligation and after 1 h were given Isolyte in the border of the infarction. The infarct + HUCBC group consisted of 38 rats that underwent LAD ligation and after 1 h were given 10 6 HUCBC in Isolyte directly into the infarct border. Immunosuppression was not given to any rat. Measurements of left ventricular (LV) ejection fraction, LV pressure, dP/dt, and infarct size were determined at baseline and 1, 2, 3, and 4 months. The ejection fraction in the controls decreased from 88 ± 3% to 78 ± 4% at 4 months ( p = 0.03) as a result of normal aging. Following infarction in the infarct + vehicle group, the ejection fraction decreased from 87 ± 4% to 51 ± 3% between 1 and 4 months ( p < 0.01). In contrast, the ejection fraction of the infarcted + HUCBC-treated rat hearts decreased from 87 ± 4% to 63 ± 3% at 1 month, but progressively increased to 69 ± 6% at 3 and 4 months, which was different from infarct + vehicle group rats ( p < 0.02) but similar to the controls. At 4 months, anteroseptal wall thickening in infarct + HUCBC group was 57.9 ± 11.6%, which was nearly identical to the control anteroseptal thickening of 59.2 ± 8.9%, but was significantly greater than the infarct + vehicle group, which was 27.8 ± 7% ( p < 0.02). dP/dt max increased by 130% in controls with 5.0 µg of phenylephrine (PE)/min ( p < 0.001). In the infarct + vehicle group, dP/dt max increased by 91% with PE ( p = 0.01). In contrast, in the infarct + HUCBC group, dP/dt max increased with PE by 182% ( p < 0.001), which was significantly greater than the increase in dP/dt max in the infarct + vehicle group ( p = 0.03) and similar to the increase in the controls. Infarct sizes in the infarct + HUCBC group were smaller than the infarct + vehicle group and averaged 3.0 ± 2.8% for the infarct + HUCBC group versus 22.1 ± 5.6% for infarct + vehicle group at 3 months ( p < 0.01); at 4 months they averaged 9.2 ± 2.0% for infarct + HUCBC group versus 40.0 ± 9.2% for the infarct + vehicle group ( p < 0.001). The present experiments demonstrate that HUCBC substantially reduce infarction size in rats without requirements for immunosuppression. As a consequence, LV function measurements, determined by LV ejection fraction, wall thickening, and dP/dt, are significantly greater than the same measurements in rats with untreated infarctions.

Human Umbilical Cord Blood Progenitor Cells are Attracted to Infarcted Myocardium and Significantly Reduce Myocardial Infarction Size

“…MCP-1 and MIP play major roles in the chemoattracwhen measured at 4-5 months after the coronary occlusions and were similar to normal, unoperated control rats tion of monocytes to an inflammatory focus. MCP-1 is a potent chemoattractant for macrophages, T cells and of the same age (20). Moreover, neither the HUCBCtreated rats in our initial study nor the rats in the present natural killer cells, cytokine synthesis, reperfusion injury, and formation of granulation tissue in the healing study received any immunosuppressive therapy.…”

“…Serum concentrations of TNF-α after acute myocardial infarction correlate with collagen we injected 1 million HUCBC directly into infarcted myocardium of rats after permanent coronary occlusion deposition in the heart and with increased LV end-diastolic diameter (35). Moreover, TNF-α in combination with and observed after 1 to 3-4 months the presence of HUCBC and infarction sizes in the HUCBC-treated rats IFN-γ promotes induction of intercellular adhesion molecule-1 (ICAM-1), neutrophil adhesion to myocytes and that were significantly smaller than untreated infarcted rat hearts (20). The reduction in infarction sizes in the endothelial cells, and cell dysfunction (22).…”

“…We have recently begun to investigate the use of cells and matrix metalloproteinases, induces apoptosis, depresses LV function, and ultimately causes ventricular HUCBC as a source of stem cells for the treatment of acute myocardial infarction (20,21). In our initial study, remodeling (19,29).…”

“…Our initial results in rats with acute myocardial infarction indicate that HUCBC, when directly Care and Use of Laboratory Animals of the National Institutes of Health. Forty-five male Sprague-Dawley injected into infarcted myocardium, significantly limit infarct size and improve left ventricular function but do rats (Harlan) weighing between 150 and 200 g were anesthetized with 3-5% isoflurane by inhalation, intubated, not stimulate an immunological rejection response (20). We therefore sought in the present investigation to deand placed on mechanical ventilation with continuous isoflurane and oxygen.…”

“…This resuspension and centrifugation step was repeated three more times. heart failure (20). Because 4 million births occur each year in the US, there is a tremendous resource of human After decanting the final 10 ml of PBS, the cell pellet was resuspended in 1 ml saline and placed on ice.…”