Experimental protocol. Three groups of pigs were studied (groups I–III). Four days after a baseline echocardiogram, pigs underwent a 90-minute coronar...Show More
Experimental protocol. Three groups of pigs were studied (groups I–III). Four days after a baseline echocardiogram, pigs underwent a 90-minute coronary occlusion followed by reperfusion or sham surgery. At 3 to 4 months after MI (97±12 days in vehicle-treated and 96±6 days in CSC-treated groups), pigs received intracoronary infusion of vehicle (group II), or autologous CSCs into the infarct-related artery by the use of a balloon catheter (group III). Group I served as noninfarcted controls. Echocardiographic and hemodynamic assessment of cardiac function was performed before treatment and at the time of euthanasia. At 31 days after vehicle/CSC therapy, pigs were euthanized for morphometric and histological studies. BSL indicates baseline; Cath, at the time of catheterization; CSC, cardiac stem cell; echo, echocardiogram; and MI, myocardial infarction.Show Less
Plasma troponin T (A) and CK-MB (B) levels at baseline (−1), immediately after intracoronary cell/vehicle delivery (0), and 6, 12, 24, and 48 hours after delivery. Data are means±SEM. CSC indicates cardiac stem cell; CK-MB, creatine kinase MB fraction; and SEM, standard error of the mean.
Assessment of LV function before and after vehicle or CSC therapy: hemodynamic variables (LV end-diastolic pressure [A] and LV dP/dtmax [B]), representative M-mode echocardiographic images at 30 days after treatment in pigs that were given vehicle (C) and CSCs (D), and quantitative echocardiographic analysis of LV function (infarct wall thickening fraction and ejection fraction) (E and F). In comparison with the vehicle-treated pig, the CSC-treated animal exhibited a smaller LV cavity, a thicker infarcted wall, and improved motion of the infarcted wall (C and D). Quantitative echocardiographic analysis shows improvement in LV functional parameters at 30 days after CSC treatment (E and F). Data are means±SEM. * P<0.05 vs noninfarcted controls; §P<0.05 vs vehicle-treated pigs (unpaired t test). Cath indicates at the time of catheterization; CSC, cardiac stem cell; LV, left ventricular; and LVEDP, LV end-diastolic pressure.
Impact of CSC therapy on LV anatomy. Representative transverse sections of hearts from a vehicle-treated (A) and a CSC-treated (B) pig after 30 days of follow-up. Scar tissue (whitish patch) is highlighted in both the sections. Note that the scar area is smaller and the infarct wall thicker in the CSC-treated heart. CSC indicates cardiac stem cell; and LV, left ventricular.
Representative slides of transmural blocks from the core infarct zone from a vehicle-treated (A) and a CSC-treated (B) pig after 30 days of follow-up (hematoxylin and eosin stain). C shows a higher magnification of the section from a CSC-treated pig. A, Dense transmural fibrosis in a vehicle-treated pig with a homogeneous pattern of scar with less viable tissue; B and C, Mid wall fibrosis surrounded by thick viable myocyte bundles in a pig treated with CSCs. CSC indicates cardiac stem cell.
Representative confocal microscopic image from a CSC-treated pig showing small cycling Ki67-positive myocytes in the infarcted region at 30 days after...Show More
Representative confocal microscopic image from a CSC-treated pig showing small cycling Ki67-positive myocytes in the infarcted region at 30 days after CSC infusion. Positivity for α-sarcomeric actin (red) identifies cardiomyocytes. CSC indicates cardiac stem cell; and α-sarc. actin, α-sarcomeric actin.Show Less
