Sonic Hedgehog upregulation does not enhance the survival and engraftment of stem cell-derived cardiomyocytes in infarcted hearts

Autoři: Jill J. Weyers aff001;  Jagadambika J. Gunaje aff001;  Benjamin Van Biber aff001;  Amy Martinson aff001;  Hans Reinecke aff001;  William M. Mahoney aff001;  Stephen M. Schwartz aff001;  Timothy C. Cox aff002;  Charles E. Murry aff001
Působiště autorů: Department of Pathology, Center for Cardiovascular Biology, and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, United States of America aff001;  Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington, United States of America aff002;  Department of Pediatrics, University of Washington, Seattle, Washington, United States of America aff003;  Department of Medicine/Cardiology, University of Washington, Seattle, Washington, United States of America aff004;  Department of Bioengineering, University of Washington, Seattle, Washington, United States of America aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227780


The engraftment of human stem cell-derived cardiomyocytes (hSC-CMs) is a promising treatment for remuscularizing the heart wall post-infarction, but it is plagued by low survival of transplanted cells. We hypothesize that this low survival rate is due to continued ischemia within the infarct, and that increasing the vascularization of the scar will ameliorate the ischemia and improve hSC-CM survival and engraftment. An adenovirus expressing the vascular growth factor Sonic Hedgehog (Shh) was injected into the infarcted myocardium of rats immediately after ischemia/reperfusion, four days prior to hSC-CM injection. By two weeks post-cell injection, Shh treatment had successfully increased capillary density outside the scar, but not within the scar. In addition, there was no change in vessel size or percent vascular volume when compared to cell injection alone. Micro-computed tomography revealed that Shh failed to increase the number and size of larger vessels. It also had no effect on graft size or heart function when compared to cell engraftment alone. Our data suggests that, when combined with the engraftment of hSC-CMs, expression of Shh within the infarct scar and surrounding myocardium is unable to increase vascularization of the infarct scar, and it does not improve survival or function of hSC-CM grafts.

Klíčová slova:

Capillaries – Cardiomyocytes – Heart – Hedgehog signaling – Histology – Myocardial infarction – Myocardium – RNA viruses


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