Abstract 17398: In Depth Evaluation of Transplanted Cardiac Myocytes Derived From Induced Pluripotent Stem Cells on the Chronic Infarct Heart in vivo in Rat
Background: In vitro expanded beating cardiac myocytes derived from induced pluripotent stem cells (iPSC-CMs) are promising source of regeneration therapy for damaged myocardium. Meanwhile, cell-sheet method has been shown to possibly maximize survival, functionality and integration of the transplanted cells into the damaged myocardium. It is hypothesized that transplanted iPSC-CMs in a cell-sheet manner may contribute to functional recovery via mechanical effects on chronic myocardial infarction (MI) heart.
Methods: F344 Nude rats were left coronary artery-ligated for 2 weeks, followed by transplantation of iPSC-CMs cell-sheets of murine origin over the infarct heart surface. Effects of the treatment were assessed including in vivo molecular/cellular imaging using third generation synchrotron radiation.
Results: Ejection fraction and activation recovery interval were significantly greater from day 3 onwards after iPSC-CMs transplantation compared to those after sham operation. A number of transplanted iPSC-CMs, which were labelled by DS-red, were present on the heart surface expressing cardiac myosin or connexin43 over 2 weeks, assessed by immunoconfocal microscopy, while mitochondorias in the the transplanted iPSC-CMs gradually showed mature structure assessed by electronmicroscopy. Of note, X-ray diffraction by the synchrotron system identified 1,0 and 1,1 equatorial reflections attributable to myosin and actin-myosin lattice planes typical of cardiac muscle fibres within the transplanted cell-sheets at 4 weeks (Figure), suggesting cyclic systolic myosin mass transfer to actin filaments in the transplanted iPSC-CMs.
Conclusions: Transplantation of iPSC-CM cell-sheets into the heart yielded functional and electrical recovery with cyclic contraction of transplanted cells in a rat chronic MI heart, indicating that this strategy may be a promising “cardiac muscle replacement” therapy.
- © 2013 by American Heart Association, Inc.