scholarly journals Retention and Functional Effect of Adipose-Derived Stromal Cells Administered in Alginate Hydrogel in a Rat Model of Acute Myocardial Infarction

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Bjarke Follin ◽  
Adam Ali Ghotbi ◽  
Andreas Ettrup Clemmensen ◽  
Simon Bentsen ◽  
Morten Juhl ◽  
...  

Background. Cell therapy for heart disease has been proven safe and efficacious, despite poor cell retention in the injected area. Improving cell retention is hypothesized to increase the treatment effect. In the present study, human adipose-derived stromal cells (ASCs) were delivered in an in situ forming alginate hydrogel following acute myocardial infarction (AMI) in rats. Methods. ASCs were transduced with luciferase and tested for ASC phenotype. AMI was inducted in nude rats, with subsequent injection of saline (controls), 1 × 106 ASCs in saline or 1 × 106 ASCs in 1% (w/v) alginate hydrogel. ASCs were tracked by bioluminescence and functional measurements were assessed by magnetic resonance imaging (MRI) and 82rubidium positron emission tomography (PET). Results. ASCs in both saline and alginate hydrogel significantly increased the ejection fraction (7.2% and 7.8% at 14 days and 7.2% and 8.0% at 28 days, resp.). After 28 days, there was a tendency for decreased infarct area and increased perfusion, compared to controls. No significant differences were observed between ASCs in saline or alginate hydrogel, in terms of retention and functional salvage. Conclusion. ASCs improved the myocardial function after AMI, but administration in the alginate hydrogel did not further improve retention of the cells or myocardial function.

1975 ◽  
Vol 35 (1) ◽  
pp. 173 ◽  
Author(s):  
P. Theroux ◽  
S. Sosayama ◽  
V. Massullo ◽  
S.W. Kemper ◽  
C. Bloor ◽  
...  

2020 ◽  
Vol 26 (1) ◽  
pp. 88-99
Author(s):  
Vasileios Sousonis ◽  
Titika Sfakianaki ◽  
Argirios Ntalianis ◽  
Ioannis Nanas ◽  
Christos Kontogiannis ◽  
...  

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.


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