Intracoronary infusion of autologous mononuclear cells from bone marrow or granulocyte colony-stimulating factor-mobilized apheresis product may not improve remodelling, contractile function, perfusion, or infarct size in a swine model of large myocardial infarction

Abstract

Intracoronary infusion of mononuclear cells from either BM or G-CSF-mobilized apheresis product may not improve or limit deterioration in systolic function, adverse ventricular remodelling, infarct size, or perfusion in a swine model of large MI.

Differential Effects of Progenitor Cell Populations on Left Ventricular Remodeling and Myocardial Neovascularization After Myocardial Infarction

“…To distinguish autocrine versus paracrine effects of infused cells, we used robust molecular labeling strategies in combination with dual photon laser microscopy of the infarct core and border zones. We did not detect engrafted or transdifferentiated MSCs 6 weeks after injection in the IRA, consistent with recent reports from several laboratories that have suggested indirect vasculogenic effects or stimulatory effects on endogenous resident stem cells (17)(18)(19). Loss of plasticity of infused allogeneic MSCs after lentiviral infection or multiple in vitro passages or impaired growth factor synthesis capacity is unlikely, as evidenced in osteogenic and adipogenic differentiation assays and secretome analysis.…”

Granulocyte-colony Stimulating Factor Treatment of Chronic Myocardial Infarction

“…In this context, Werneck-de-Castro et al [13] demonstrated that the administration of high doses of G-CSF early after MI failed to improve cardiac function at rest or under exercise stress in rats. Similar negative results were observed in mice [14], rats [15], porcine [16] and baboons [17]. Surprisingly, G-CSF administration resulted in LV enlargement and enhanced myocardial fibrosis [15].…”

Intravenous Followed by X-ray Fused with MRI-Guided Transendocardial Mesenchymal Stem Cell Injection Improves Contractility Reserve in a Swine Model of Myocardial Infarction

“…Longer follow-up was not possible as these swine become too large for MRI. Although the sample size is small compared to human efficacy trials, it is comparable to other published large animal translational studies [27, 33, 49, 50]. Our study exploited highly sensitive and reproducible endpoints such as quantitative cardiac MRI, invasive pressure-volume hemodynamics, implanted VT monitoring, and systematic histopathology to compensate for the small sample size.…”

“…Closed chest antero-septal MI was induced in 36 female Yorkshire swine weighing 30 kg using methods previously described by our group [26, 27]. Briefly, animals were sedated with an intramuscular injection of Telazol 4–6 mg/kg and Xylazine 2 mg/kg and then intubated and mechanically ventilated with1–3 % isoflurane.…”