Induced pluripotent stem cell intervention rescues ventricular wall motion disparity, achieving biological cardiac resynchronization post-infarction

Satsuki Yamada, Timothy J Nelson, Garvan M Kane, Almudena Martinez-Fernandez, Ruben J. Crespo-Diaz, Yasuhiro H Ikeda, Carmen M Terzic, Andre Terzic

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Dyssynchronous myocardial motion aggravates cardiac pump function. Cardiac resynchronization using pacing devices is a standard-of-care in the management of heart failure. Post-infarction, however, scar tissue formation impedes the efficacy of device-based therapy. The present study tests a regenerative approach aimed at targeting the origin of abnormal motion to prevent dyssynchronous organ failure. Induced pluripotent stem (iPS) cells harbour a reparative potential, and were here bioengineered from somatic fibroblasts reprogrammed with the stemness factors OCT3/4, SOX2, KLF4, and c-MYC. In a murine infarction model, within 30 min of coronary ligation, iPS cells were delivered to mapped infarcted areas. Focal deformation and dysfunction underlying progressive heart failure was resolved prospectively using speckle-tracking imaging. Tracked at high temporal and spatial resolution, regional iPS cell transplantation restored, within 10 days post-infarction, the contractility of targeted infarcted foci and nullified conduction delay in adjacent non-infarcted regions. Local iPS cell therapy, but not delivery of parental fibroblasts or vehicle, prevented or normalized abnormal strain patterns correcting the decrease in peak strain, disparity of time-to-peak strain, and pathological systolic stretch. Focal benefit of iPS cell intervention translated into improved left ventricular conduction and contractility, reduced scar, and reversal of structural remodelling, protecting from organ decompensation. Thus, in ischaemic cardiomyopathy, targeted iPS cell transplantation synchronized failing ventricles, offering a regenerative strategy to achieve biological resynchronization.

Original languageEnglish (US)
Pages (from-to)4335-4349
Number of pages15
JournalJournal of Physiology
Volume591
Issue number17
DOIs
StatePublished - Sep 2013

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Induced Pluripotent Stem Cells
Cardiac Resynchronization Therapy
Infarction
Stem Cell Transplantation
Cicatrix
Heart Failure
Fibroblasts
Equipment and Supplies
Standard of Care
Cell- and Tissue-Based Therapy
Cardiomyopathies
Ligation

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)

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Induced pluripotent stem cell intervention rescues ventricular wall motion disparity, achieving biological cardiac resynchronization post-infarction. / Yamada, Satsuki; Nelson, Timothy J; Kane, Garvan M; Martinez-Fernandez, Almudena; Crespo-Diaz, Ruben J.; Ikeda, Yasuhiro H; Terzic, Carmen M; Terzic, Andre.

In: Journal of Physiology, Vol. 591, No. 17, 09.2013, p. 4335-4349.

Research output: Contribution to journalArticle

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