TY - JOUR
T1 - Widespread myocardial delivery of heart-derived stem cells by nonocclusive triple-vessel intracoronary infusion in porcine ischemic cardiomyopathy
T2 - Superior attenuation of adverse remodeling documented by magnetic resonance imaging and histology
AU - Tseliou, Eleni
AU - Kanazawa, Hideaki
AU - Dawkins, James
AU - Gallet, Romain
AU - Kreke, Michelle
AU - Smith, Rachel
AU - Middleton, Ryan
AU - Valle, Jackelyn
AU - Marbán, Linda
AU - Kar, Saibal
AU - Makkar, Rajendra
AU - Marbán, Eduardo
N1 - Funding Information:
This work was supported by the Cedars-Sinai Board of Governors Heart Stem Cell Center. The Cedars-Sinai Board of Governors Heart Stem Cell Center provided support in the form of salaries for authors ET, HK, JD, JV, RM, RM, SK and EM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. RS, LM and MK are employed by Capricor Inc but did not participate in the funding of this study nor did they play a role in the study design, data collection, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2016 Tseliou et al.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0144523
DO - 10.1371/journal.pone.0144523
M3 - Article
C2 - 26784932
AN - SCOPUS:84958212940
SN - 1932-6203
VL - 11
JO - PLoS One
JF - PLoS One
IS - 1
M1 - e0144523
ER -