Widespread myocardial delivery of heart-derived stem cells by nonocclusive triple-vessel intracoronary infusion in porcine ischemic cardiomyopathy: Superior attenuation of adverse remodeling documented by magnetic resonance imaging and histology

Eleni Tseliou, Hideaki Kanazawa, James Dawkins, Romain Gallet, Michelle Kreke, Rachel Smith, Ryan Middleton, Jackelyn Valle, Linda Marbán, Saibal Kar, Rajendra Makkar, Eduardo Marbán

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Single-vessel, intracoronary infusion of stem cells under stop-flow conditions has proven safe but achieves only limited myocardial coverage. Continuous flow intracoronary delivery to one or more coronary vessels may achieve broader coverage for treating cardiomyopathy, but has not been investigated. Using nonocclusive coronary guiding catheters, we infused allogeneic cardiosphere-derived cells (CDCs) either in a single vessel or sequentially in all three coronary arteries in porcine ischemic cardiomyopathy and used magnetic resonance imaging (MRI) to assess structural and physiological outcomes. Vehicle-infused animals served as controls. Single-vessel stop-flow and continuous-flow intracoronary infusion revealed equivalent effects on scar size and function. Sequential infusion into each of the three major coronary vessels under stop-flow or continuous-flow conditions revealed equal efficacy, but less elevation of necrotic biomarkers with continuous-flow delivery. In addition, multi-vessel delivery resulted in enhanced global and regional tissue function compared to a triple-vessel placebo-treated group. The functional benefits after global cell infusion were accompanied histologically by minimal inflammatory cellular infiltration, attenuated regional fibrosis and enhanced vessel density in the heart. Sequential multi-vessel non-occlusive delivery of CDCs is safe and provides enhanced preservation of left ventricular function and structure. The current findings provide preclinical validation of the delivery method currently undergoing clinical testing in the Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial of CDCs in heart failure patients.

Original languageEnglish
Article numbere0144523
JournalPLoS One
Volume11
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

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Histology
cardiomyopathy
Magnetic resonance
Stem cells
Cardiomyopathies
magnetic resonance imaging
histology
stem cells
Swine
Stem Cells
heart
Magnetic Resonance Imaging
Imaging techniques
swine
Coronary Vessels
coronary vessels
Catheters
Biomarkers
Infiltration
Animals

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Widespread myocardial delivery of heart-derived stem cells by nonocclusive triple-vessel intracoronary infusion in porcine ischemic cardiomyopathy : Superior attenuation of adverse remodeling documented by magnetic resonance imaging and histology. / Tseliou, Eleni; Kanazawa, Hideaki; Dawkins, James; Gallet, Romain; Kreke, Michelle; Smith, Rachel; Middleton, Ryan; Valle, Jackelyn; Marbán, Linda; Kar, Saibal; Makkar, Rajendra; Marbán, Eduardo.

In: PLoS One, Vol. 11, No. 1, e0144523, 01.01.2016.

Research output: Contribution to journalArticle

Tseliou, Eleni ; Kanazawa, Hideaki ; Dawkins, James ; Gallet, Romain ; Kreke, Michelle ; Smith, Rachel ; Middleton, Ryan ; Valle, Jackelyn ; Marbán, Linda ; Kar, Saibal ; Makkar, Rajendra ; Marbán, Eduardo. / Widespread myocardial delivery of heart-derived stem cells by nonocclusive triple-vessel intracoronary infusion in porcine ischemic cardiomyopathy : Superior attenuation of adverse remodeling documented by magnetic resonance imaging and histology. In: PLoS One. 2016 ; Vol. 11, No. 1.
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