Double Trouble: A Case Of Combined Amyloid And Ischemic Cardiomyopathy
HFSA ePoster Library. Bosah A. 09/10/21; 343654; 94
Arinze Bosah
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Abstract
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Stem/progenitor cells are usually cultured at atmospheric O2 tension (21%). Since physiologic O2 tension in the heart is ~5%, using 21% O2 may cause oxidative stress and toxicity. Cardiac mesenchymal cells (CMCs), a newly discovered and promising type of progenitor cells, are effective in improving left ventricle (LV) function after myocardial infarction (MI). We have previously shown that, compared with 21% O2, culture at 5% O2 increases CMC proliferation, telomerase activity, telomere length, resistance to severe hypoxia in vitro and results in greater functional improvement in the failing heart (two independent assayed by echocardiography and hemodynamics) at 35 days after cell transplantation in vivo. However, the effects of 5% O2 cultured CMCs on the structure of the failing heart are unknown. Therefore, murine CMCs were cultured at 21% or 5% O2. Mice with heart failure caused by a 60-min coronary occlusion followed by 30 days of reperfusion received vehicle, 21% or 5% O2 CMCs via echocardiography-guided intraventricular injection. After 35 days, compared with the vehicle group, the 5% O2 CMC-treated hearts exhibited a decrease in scar size and a concomitant increase in the amount of viable myocardium in the risk region (assessed by trichrome staining) (Figure A-C), concomitant with an increase in LV anterior wall (infarct wall) thickness, a decrease in LV posterior wall (noninfarcted wall) thickness, and a decrease in LV expansion index (that is indicative of reduced LV dilatation). In contrast, the 21% O2 CMC-treated hearts did not differ significantly from the vehicle-treated hearts with respect to scar size, viable myocardium, or noninfarcted wall thickness. As shown in Figure D-H (assayed by picrosirius red staining and polarized light microscopy), at 35 days after cell therapy, collagen content in the heart was not significantly different in the 21% O2 CMC group compared with the vehicle group. In contrast, collagen content was significantly reduced in hearts treated with 5% O2 grown CMCs as compared with the vehicle group (40.1±3.8% of risk region vs. 51.6±4.7%, P<0.05; 9.4±2.1% of noninfarcted region vs.15.7±1.9%, P<0.05 - a relative reduction of nearly 50%). 5% O2 grown CMCs, but not 21% O2 grown CMCs, significantly decreased scar size, increased viable myocardium, reduced LV dilatation, and limited myocardial fibrosis both in the risk and noninfarcted regions of failing hearts. These data indicate, for the first time, that culturing CMCs at physiologic (5%) O2 tension provides superior therapeutic efficacy in ameliorating cardiac remodeling via morphologic improvement in the failing heart.
Stem/progenitor cells are usually cultured at atmospheric O2 tension (21%). Since physiologic O2 tension in the heart is ~5%, using 21% O2 may cause oxidative stress and toxicity. Cardiac mesenchymal cells (CMCs), a newly discovered and promising type of progenitor cells, are effective in improving left ventricle (LV) function after myocardial infarction (MI). We have previously shown that, compared with 21% O2, culture at 5% O2 increases CMC proliferation, telomerase activity, telomere length, resistance to severe hypoxia in vitro and results in greater functional improvement in the failing heart (two independent assayed by echocardiography and hemodynamics) at 35 days after cell transplantation in vivo. However, the effects of 5% O2 cultured CMCs on the structure of the failing heart are unknown. Therefore, murine CMCs were cultured at 21% or 5% O2. Mice with heart failure caused by a 60-min coronary occlusion followed by 30 days of reperfusion received vehicle, 21% or 5% O2 CMCs via echocardiography-guided intraventricular injection. After 35 days, compared with the vehicle group, the 5% O2 CMC-treated hearts exhibited a decrease in scar size and a concomitant increase in the amount of viable myocardium in the risk region (assessed by trichrome staining) (Figure A-C), concomitant with an increase in LV anterior wall (infarct wall) thickness, a decrease in LV posterior wall (noninfarcted wall) thickness, and a decrease in LV expansion index (that is indicative of reduced LV dilatation). In contrast, the 21% O2 CMC-treated hearts did not differ significantly from the vehicle-treated hearts with respect to scar size, viable myocardium, or noninfarcted wall thickness. As shown in Figure D-H (assayed by picrosirius red staining and polarized light microscopy), at 35 days after cell therapy, collagen content in the heart was not significantly different in the 21% O2 CMC group compared with the vehicle group. In contrast, collagen content was significantly reduced in hearts treated with 5% O2 grown CMCs as compared with the vehicle group (40.1±3.8% of risk region vs. 51.6±4.7%, P<0.05; 9.4±2.1% of noninfarcted region vs.15.7±1.9%, P<0.05 - a relative reduction of nearly 50%). 5% O2 grown CMCs, but not 21% O2 grown CMCs, significantly decreased scar size, increased viable myocardium, reduced LV dilatation, and limited myocardial fibrosis both in the risk and noninfarcted regions of failing hearts. These data indicate, for the first time, that culturing CMCs at physiologic (5%) O2 tension provides superior therapeutic efficacy in ameliorating cardiac remodeling via morphologic improvement in the failing heart.
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