title: Intrapericardial Delivery of Cardiosphere-Derived Cells: An Immunological Study in a Clinically Relevant Large Animal Model.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  CDCs 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.
  
  
  RESULTS
  Our 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.
  
  
  CONCLUSIONS
  The 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.
authors: Stem Cell Therapy Unit, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres, Spain.
authors: Rebeca
authors: R
authors: Blázquez
authors: Stem Cell Therapy Unit, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres, Spain.
authors: Francisco Miguel
authors: FM
authors: Sánchez-Margallo
authors: Endoluminal Therapy and Diagnosis, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres, Spain.
authors: Verónica
authors: V
authors: Crisóstomo
authors: Endoluminal Therapy and Diagnosis, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres, Spain.
authors: Claudia
authors: C
authors: Báez
authors: Endoluminal Therapy and Diagnosis, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres, Spain.
authors: Juan
authors: J
authors: Maestre
authors: Stem Cell Therapy Unit, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres, Spain.
authors: Verónica
authors: V
authors: Álvarez
authors: Stem Cell Therapy Unit, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres, Spain.
authors: Javier G
authors: JG
authors: Casado
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D017690:Cell Transplantation; D019902:Chondrocytes / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008279:Magnetic Resonance Imaging; D009203:Myocardial Infarction / Q000276:immunology* / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000276:immunology; D010012:Osteogenesis; D010496:Pericardium / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods; D013552:Swine
chemical_list: D016207:Cytokines