Human Cord Blood Mononuclear Cells Decrease Cytokines and Inflammatory Cells in Acute Myocardial Infarction

Abstract

We investigated whether human umbilical cord blood mononuclear cells (HUCBC), which contain hematopoietic and mesenchymal progenitor cells, can limit myocardial cytokine expression and inflammatory cell infiltration in acute myocardial infarction. We permanently ligated the left coronary artery of rats and injected into the myocardium either Isolyte or 4 x 10(6) HUCBC in Isolyte and measured myocardial cytokines with antibody arrays at 2, 6, 12, 24, and 72 hours after infarction. We then measured with flow cytometry myocardial macrophages, neutrophils and lymphocytes at 12, 24, and 72 hours after infarctions in rats treated with either intramyocardial Isolyte or 4 x 10(6) HUCBC. In the Isolyte-treated hearts, between 2 and 12 hours after myocardial infarction, tumor necrosis factor-alpha increased from 6.7 +/- 0.9% to 52.3 +/- 4.7%, monocyte chemoattract protein increased from 9.5 +/- 1.2% to 39.8 +/- 2.1%, fractalkine increased from 11 +/- 1.5% to 28.1 +/- 1.3%, ciliary neurotrophic factor increased from 12.1 +/- 0.02% to 25.9 +/- 1.1%, macrophage inflammatory protein increased from 10.3 +/- 1.5% to 23.9.0 +/- 1.4%, interferon-gamma increased from 8.7 +/- 0.4% to 26.0 +/- 1.6%, interleukin-1beta increased from 6.1 +/- 0.04% to 19.0 +/- 1.2%, and IL-4 increased from 5.9 +/- 0.03% to 15 +/- 1.5% (all p< 0.001 compared with controls). The concentrations of fractalkine remained significantly increased at 72 hours after acute infarction. In contrast, the myocardial concentrations of these cytokines did not significantly change in HUCBC treated hearts at 2, 6, 12, 24, or 72 hours after infarction. The percentage of neutrophils increased from 0.04 +/- 0.2%/50,000 heart cells in the controls to 5.3 +/- 1.2%/50,000 heart cells 12 hours after infarction in Isolyte-treated hearts but averaged only 1.3 +/- 0.7%/50,000 heart cells in HUCBC treated hearts (p < 0.02). Thereafter, the percentages of neutrophils rapidly decreased at 24 and at 72 hours after infarction and averaged 0.6 +/- 0.2%/50,000 heart cells at 72 hours after infarction in Isolyte-treated hearts in contrast to 0.2 +/- 0.1%/50,000 cells in HUCBC hearts (p < 0.05). Moreover, the percentages of neutrophils at 24 and 72 hours in HUCBC hearts were not significantly different from controls. At 24 hours post infarction, the percentage of CD3 and CD4 lymphocytes were 10.7 +/- 1.4% and 6.3 +/- 1.1%/50,000 cells in Isolyte hearts in comparison with only 4.9 +/- 0.8% and 2.9 +/- 0.5% in HUCBC hearts (p < 0.005 for Isolyte versus HUCBC). The percentage of CD11b macrophages was 2.8 +/- 0.3% in Isolyte hearts and 1.9 +/- 0.2% in HUCBC treated hearts (p < 0.05). At 72 hours after infarction, the percentage of CD3 and CD4 lymphocytes averaged 8.0 +/- 1.1% and 5.1 +/- 0.8%/50,000 heart cells in Isolyte hearts in comparison with only 4.1 +/- 0.5% and 2.3 +/- 0.4%/50,000 heart cells in the HUCBC treated infarctions (p < 0.005). Left ventricular infarct sizes in Isolyte-treated hearts at 72 hours post infarction averaged 15.7 +/- 1.4% of the left ventricular muscle area in cont...

G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

“…hUCB stem cells have also been used experimentally in animal models of TBI. In some studies, transplanted cells derived from the mononuclear fraction of hUCB conferred neuroprotection by decreasing inflammation and brain tissue loss, promoting neurogenesis, and rescue of neurological dysfunctions (e.g., 11,41,78). Additionally, mesenchymal stem cells (MSCs) derived from hUCB promoted functional benefits by increasing angiogenesis and vasculogenesis (1,53,55).…”

Human Umbilical Cord Blood Stem Cells and Chitosan Hydrogels Produce Similar Beneficial Effects in Acute Myocardial Infarctions and Ischemic Cardiomyopathies

“…Moreover, this paracrine action of hUCBC is increased 50 to 100% during severe hypoxia and in the presence of free oxygen radicals [20,24]. This paracrine action of hUCBC can suppress in the ischemic myocardium the inflammatory cytokines tumor necrosis factor-alpha, monocyte chemoattraction protein and macrophage inflammatory protein by more than 50% [25]. Cord blood stem cells can also limit or inhibit caspase expression and the caspase cascade in the myocardium that otherwise contributes to myocardial inflammation and myocyte death after coronary artery occlusion [26].…”

“…By stimulating fibroblast migration into infarctions and increasing collagen production, chitosan can increase infarct scar thickness which we observed in the present investigation. Increased scar thickness, especially in the infarct perimeter, can also limit the seepage of pro-introphils by 75% and lymphocytes by more than 50% that otherwise release inflammatory cytokines that cause myocardial inflammation and necrosis [25,27].…”

Advances in Regenerative Medicine

“…Implantation of HUCB cells into infarcted myocardium of non-immunosuppressed rats within 2 or at 24 hours after LAD occlusion, limited the expression of pro-inflammatory cytokines such as TNF-α, MCP-1, MIP-1α, and IFN-γ in the infarcted myocardium and it may be associated with significant decreases in infarct volume. Further analysis was carried out by transplanting 4 x 10 6 cells and performing cytokine analysis and inflammatory cell recruitment at 2, 6, 12, 24 and 72 hours after LAD ligation (Henning et al, 2008). They observed that the infiltration of inflammatory cells and secretion of inflammatory cytokines was significantly reduced by HUCB cells within 2 hours compared to non-treatment after LAD occlusion and this was maintained through to 72 hours.…”