TY - JOUR
T1 - Human Induced Pluripotent Stem Cell–Derived Cardiomyocyte Patch in Rats With Heart Failure
AU - Lancaster, Jordan J.
AU - Sanchez, Pablo
AU - Repetti, Giuliana G.
AU - Juneman, Elizabeth
AU - Pandey, Amitabh C.
AU - Chinyere, Ikeotunye R.
AU - Moukabary, Talal
AU - LaHood, Nicole
AU - Daugherty, Sherry L.
AU - Goldman, Steven
N1 - Publisher Copyright:
© 2019 The Society of Thoracic Surgeons
PY - 2019/10
Y1 - 2019/10
N2 - Background: To treat chronic heart failure (CHF), we developed a robust, easy to handle bioabsorbable tissue-engineered patch embedded with human neonatal fibroblasts and human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs). This patch was implanted on the epicardial surface of the heart covering the previously infarcted tissue. Methods: Sprague-Dawley rats (6-8 weeks old) underwent sham surgery (n = 12) or left coronary artery ligation (n = 45). CHF rats were randomized 3 weeks after ligation to CHF control with sham thoracotomy (n = 21), or a fibroblasts/hiPSC-CMs patch (n = 24) was implanted. All sham surgery rats also underwent a sham thoracotomy. At 3 weeks after randomization, hemodynamics, echocardiography, electrophysiologic, and cell survival studies were performed. Results: Patch-treated rats had decreased (P < .05) left ventricular-end diastolic pressure and the time constant of left ventricular relaxation (Tau), increased anterior wall thickness in diastole, and improved echocardiography-derived indices of diastolic function (E/e’ [ratio of early peak flow velocity to early peak LV velocity] and e’/a’ [ratio of early to late peak left ventricular velocity]). All rats remained in normal sinus rhythm, with no dysrhythmias. Rats treated with the patch showed improved electrical activity. Transplanted hiPSC-CMs were present at 7 days but not detected at 21 days after implantation. The patch increased (P < .05) gene expression of vascular endothelial growth factor, angiopoietin 1, gap junction α-1 protein (connexin 43), β-myosin heavy 7, and insulin growth factor-1 expression in the infarcted heart. Conclusions: Epicardial implantation of a fibroblasts/hiPSC-CMs patch electrically enhanced conduction, lowered left ventricular end-diastolic pressure, and improved diastolic function in rats with CHF. These changes were associated with increases in cytokine expression.
AB - Background: To treat chronic heart failure (CHF), we developed a robust, easy to handle bioabsorbable tissue-engineered patch embedded with human neonatal fibroblasts and human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs). This patch was implanted on the epicardial surface of the heart covering the previously infarcted tissue. Methods: Sprague-Dawley rats (6-8 weeks old) underwent sham surgery (n = 12) or left coronary artery ligation (n = 45). CHF rats were randomized 3 weeks after ligation to CHF control with sham thoracotomy (n = 21), or a fibroblasts/hiPSC-CMs patch (n = 24) was implanted. All sham surgery rats also underwent a sham thoracotomy. At 3 weeks after randomization, hemodynamics, echocardiography, electrophysiologic, and cell survival studies were performed. Results: Patch-treated rats had decreased (P < .05) left ventricular-end diastolic pressure and the time constant of left ventricular relaxation (Tau), increased anterior wall thickness in diastole, and improved echocardiography-derived indices of diastolic function (E/e’ [ratio of early peak flow velocity to early peak LV velocity] and e’/a’ [ratio of early to late peak left ventricular velocity]). All rats remained in normal sinus rhythm, with no dysrhythmias. Rats treated with the patch showed improved electrical activity. Transplanted hiPSC-CMs were present at 7 days but not detected at 21 days after implantation. The patch increased (P < .05) gene expression of vascular endothelial growth factor, angiopoietin 1, gap junction α-1 protein (connexin 43), β-myosin heavy 7, and insulin growth factor-1 expression in the infarcted heart. Conclusions: Epicardial implantation of a fibroblasts/hiPSC-CMs patch electrically enhanced conduction, lowered left ventricular end-diastolic pressure, and improved diastolic function in rats with CHF. These changes were associated with increases in cytokine expression.
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U2 - 10.1016/j.athoracsur.2019.03.099
DO - 10.1016/j.athoracsur.2019.03.099
M3 - Article
C2 - 31075250
AN - SCOPUS:85071081488
SN - 0003-4975
VL - 108
SP - 1169
EP - 1177
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 4
ER -