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Epicardial delivery of collagen patches with adipose-derived stem cells in rat and minipig models of chronic myocardial infarction
Authors:Miriam Arañ  a,Juan J. Gavira,Estefaní  a Peñ  a,Arantxa Gonzá  lez,Gloria Abizanda,Myriam Cilla,Marta M. Pé  rez,Edurne Albiasu,Natalia Aguado,Mayte Casado,Begoñ  a Ló  pez,Susana Gonzá  lez,Mario Soriano,Cristina Moreno,Juana Merino,José     M. Garcí  a-Verdugo,Javier Dí  ez,Manuel Doblaré  ,Beatriz Pelacho,Felipe Prosper
Affiliation:1. Laboratory of Cell Therapy, Division of Oncology, Foundation for Applied Medical Research, University of Navarra, Spain;2. Department of Cardiology and Cardiovascular Surgery, Clinica Universidad de Navarra, University of Navarra, Spain;3. Bioengineering Division, Aragon Institute of Engineering Research, University of Zaragoza, Zaragoza, Spain;4. Laboratory of Myocardial Remodeling, Division of Cardiovascular Sciences, Foundation for Applied Medical Research, University of Navarra, Spain;5. Department of Cell Biology, Instituto Cavanilles, University of Valencia, Spain;6. Immunology Service, Clinica Universidad de Navarra, University of Navarra, Spain;g Hematology and Cell Therapy, Clinica Universidad de Navarra, University of Navarra, Spain;h Department of Anatomy, Embryology and Genetics, University of Zaragoza, Spain;i CIBER-BBN-Centro de Investigación Biomédica en Red en Bioingeniería Biomateriales y Nanomedicina, Zaragoza, Spain
Abstract:
Although transplantation of adipose-derived stem cells (ADSC) in chronic myocardial infarction (MI) models is associated with functional improvement, its therapeutic value is limited due to poor long-term cell engraftment and survival. Thus, the objective of this study was to examine whether transplantation of collagen patches seeded with ADSC could enhance cell engraftment and improve cardiac function in models of chronic MI. With that purpose, chronically infarcted Sprague–Dawley rats (n = 58) were divided into four groups and transplanted with media, collagen scaffold (CS), rat ADSC, or CS seeded with rat ADSC (CS-rADSC). Cell engraftment, histological changes, and cardiac function were assessed 4 months after transplantation. In addition, Göttingen minipigs (n = 18) were subjected to MI and then transplanted 2 months later with CS or CS seeded with autologous minipig ADSC (CS-pADSC). Functional and histological assessments were performed 3 months post-transplantation. Transplantation of CS-rADSC was associated with increased cell engraftment, significant improvement in cardiac function, myocardial remodeling, and revascularization. Moreover, transplantation of CS-pADSC in the pre-clinical swine model improved cardiac function and was associated with decreased fibrosis and increased vasculogenesis. In summary, transplantation of CS-ADSC resulted in enhanced cell engraftment and was associated with a significant improvement in cardiac function and myocardial remodeling.
Keywords:Adipose-derived stem cells (ADSC)   Collagen carriers   Myocardial infarction   Biocompatibility   Preclinical model
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