Abstract
IntroductionThe intrapericardial delivery has been defined as an efficient method for pharmacological agent delivery. Here we hypothesize that intrapericardial administration of cardiosphere-derived cells (CDCs) may have an immunomodulatory effect providing an optimal microenvironment for promoting cardiac repair. To our knowledge, this is the first report studying the effects of CDCs for myocardial repair using the intrapericardial delivery route.Material and MethodsCDCs lines were isolated, expanded and characterized by flow cytometry and PCR. Their differentiation ability was determined using specific culture media and differential staining. 300,000 CDCs/kg were injected into the pericardial space of a swine myocardial infarcted model. Magnetic resonance imaging, biochemical analysis of pericardial fluid and plasma, cytokine measurements and flow cytometry analysis were performed.ResultsOur results showed that, phenotype and differentiation behavior of porcine CDCs were equivalent to previously described CDCs. Moreover, the intrapericardial administration of CDCs fulfilled the safety aspects as non-adverse effects were reported. Finally, the phenotypes of resident lymphocytes and TH1 cytokines in the pericardial fluid were significantly altered after CDCs administration.ConclusionsThe pericardial fluid could be considered as a safe and optimal vehicle for CDCs administration. The observed changes in the studied immunological parameters could exert a modulation in the inflammatory environment of infarcted hearts, indirectly benefiting the endogenous cardiac repair.
Highlights
The intrapericardial delivery has been defined as an efficient method for pharmacological agent delivery
We hypothesize that intrapericardial administration of cardiospherederived cells (CDCs) may have an immunomodulatory effect providing an optimal microenvironment for promoting cardiac repair
Phenotype and differentiation behavior of porcine CDCs were equivalent to previously described CDCs
Summary
Once confirmed the safety aspects of intrapericardial administration using porcine CDCs, we aimed to compare the phenotype profile of resident lymphocytes in the pericardial fluid immediately before CDCs administration and 30 days post-administration (Fig 3). Apart from the analysis of leukocyte subsets and biochemical parameters in the pericardial fluid, here we aimed to determine the effect of intrapericardial administration of CDCs in the cytokine microenvironment. We aimed to quantify a commercially available panel of TH1/TH2 cytokines in pericardial fluid and plasma samples from infarcted animals with intrapericardially administered CDCs
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