TY - JOUR
TI - Intracoronary Administration of Allogeneic Cardiosphere-Derived Cells
Immediately Prior to Reperfusion in Pigs With Acute Myocardial
Infarction Reduces Infarct Size and Attenuates Adverse Cardiac
Remodeling
AU - Sousonis, Vasileios
AU - Sfakianaki, Titika
AU - Ntalianis, Argirios and
AU - Nanas, Ioannis
AU - Kontogiannis, Christos
AU - Aravantinos, Dionysios and
AU - Kapelios, Chris
AU - Katsaros, Lampros
AU - Nana, Maria
AU - Sampaziotis,
AU - Dimitrios
AU - Sanoudou, Despina
AU - Papalois, Apostolos
AU - Malliaras,
AU - Konstantinos
JO - Journal of Cardiovascular Pharmacology and Therapeutics
PY - 2021
VL - 26
TODO - 1
SP - 88-99
PB - SAGE Publications Inc.
SN - 1074-2484, 1940-4034
TODO - 10.1177/1074248420941672
TODO - cardiosphere-derived cells; allogeneic cells; no reflow; microvascular
obstruction; myocardial infarction
TODO - Background: Allogeneic cardiosphere-derived cells (CDCs) exert
cardioprotective effects when administered intracoronarily after
reperfusion in animal models of acute myocardial infarction (AMI). The
“no-reflow” phenomenon develops rapidly post-reperfusion and may
undermine the efficacy of cell therapy, due to poor cell delivery in
areas of microvascular obstruction (MVO). We hypothesized that
CDC-induced cardioprotection would be enhanced by cell administration
prior to reperfusion, when microvasculature is still relatively intact,
to facilitate widespread cell delivery within the ischemic area. Methods
and Results: We studied 81 farm pigs; 55 completed the specified
protocols. A dose-optimization study in infarcted pigs demonstrated that
the doses of 5 million and 10 million CDCs are the maximum safe doses
that can be administered intracoronarily at 5 minutes prior to and at 5
minutes post-reperfusion, respectively, without aggravating MVO.
Quantification of acute cell retention by polymerase chain reaction
demonstrated that cell delivery prior to reperfusion resulted in higher
cardiac cell retention compared to delivery post-reperfusion. We then
performed a randomized, placebo-controlled study to assess the long-term
efficacy of intracoronary infusion of 5 million allogeneic CDCs,
delivered at 5 minutes prior to reperfusion, in a porcine model of AMI.
The CDC therapy resulted in decreased scar size, improved regional
systolic function, and attenuation of adverse cardiac remodeling
(manifested as preserved global systolic function, preserved
end-systolic volume, and decreased interstitial fibrosis) compared to
placebo at 30 days post-MI. Conclusions: Dose-optimized intracoronary
infusion of allogeneic CDCs prior to reperfusion in a porcine model of
AMI is feasible, safe and confers long-term benefits.
ER -