Human Induced Pluripotent Stem Cell–Derived Cardiomyocyte Patch in Rats With Heart Failure

Jordan J. Lancaster, Pablo Sanchez, Giuliana G. Repetti, Elizabeth Juneman, Amitabh C. Pandey, Ikeotunye R. Chinyere, Talal Moukabary, Nicole LaHood, Sherry L. Daugherty, Steven Goldman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1169-1177
Number of pages9
JournalAnnals of Thoracic Surgery
Volume108
Issue number4
DOIs
StatePublished - Oct 2019

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Human Induced Pluripotent Stem Cell–Derived Cardiomyocyte Patch in Rats With Heart Failure'. Together they form a unique fingerprint.

Cite this