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Long-Term Engraftment of Human Cardiomyocytes Combined with Biodegradable Microparticles Induces Heart Repair.
Saludas, Laura; Garbayo, Elisa; Mazo, Manuel; Pelacho, Beatriz; Abizanda, Gloria; Iglesias-Garcia, Olalla; Raya, Angel; Prósper, Felipe; Blanco-Prieto, María J.
Afiliação
  • Saludas L; Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain (L.S., E.G., M.J.B.-P.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (L.S., E.G., M.M., B.P., G.A., F.P., M.J.B.-P.); Hematology and Cell Therapy, Clín
  • Garbayo E; Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain (L.S., E.G., M.J.B.-P.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (L.S., E.G., M.M., B.P., G.A., F.P., M.J.B.-P.); Hematology and Cell Therapy, Clín
  • Mazo M; Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain (L.S., E.G., M.J.B.-P.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (L.S., E.G., M.M., B.P., G.A., F.P., M.J.B.-P.); Hematology and Cell Therapy, Clín
  • Pelacho B; Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain (L.S., E.G., M.J.B.-P.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (L.S., E.G., M.M., B.P., G.A., F.P., M.J.B.-P.); Hematology and Cell Therapy, Clín
  • Abizanda G; Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain (L.S., E.G., M.J.B.-P.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (L.S., E.G., M.M., B.P., G.A., F.P., M.J.B.-P.); Hematology and Cell Therapy, Clín
  • Iglesias-Garcia O; Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain (L.S., E.G., M.J.B.-P.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (L.S., E.G., M.M., B.P., G.A., F.P., M.J.B.-P.); Hematology and Cell Therapy, Clín
  • Raya A; Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain (L.S., E.G., M.J.B.-P.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (L.S., E.G., M.M., B.P., G.A., F.P., M.J.B.-P.); Hematology and Cell Therapy, Clín
  • Prósper F; Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain (L.S., E.G., M.J.B.-P.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (L.S., E.G., M.M., B.P., G.A., F.P., M.J.B.-P.); Hematology and Cell Therapy, Clín
  • Blanco-Prieto MJ; Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain (L.S., E.G., M.J.B.-P.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (L.S., E.G., M.M., B.P., G.A., F.P., M.J.B.-P.); Hematology and Cell Therapy, Clín
J Pharmacol Exp Ther ; 370(3): 761-771, 2019 09.
Article em En | MEDLINE | ID: mdl-30728248
ABSTRACT
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are a promising cell source for cardiac repair after myocardial infarction (MI) because they offer several advantages such as potential to remuscularize infarcted tissue, integration in the host myocardium, and paracrine therapeutic effects. However, cell delivery issues have limited their potential application in clinical practice, showing poor survival and engraftment after transplantation. In this work, we hypothesized that the combination of hiPSC-CMs with microparticles (MPs) could enhance long-term cell survival and retention in the heart and consequently improve cardiac repair. CMs were obtained by differentiation of hiPSCs by small-molecule manipulation of the Wnt pathway and adhered to biomimetic poly(lactic-co-glycolic acid) MPs covered with collagen and poly(d-lysine). The potential of the system to support cell survival was analyzed in vitro, demonstrating a 1.70-fold and 1.99-fold increase in cell survival after 1 and 4 days, respectively. The efficacy of the system was tested in a mouse MI model. Interestingly, 2 months after administration, transplanted hiPSC-CMs could be detected in the peri-infarct area. These cells not only maintained the cardiac phenotype but also showed in vivo maturation and signs of electrical coupling. Importantly, cardiac function was significantly improved, which could be attributed to a paracrine effect of cells. These findings suggest that MPs represent an excellent platform for cell delivery in the field of cardiac repair, which could also be translated into an enhancement of the potential of cell-based therapies in other medical applications.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Miócitos Cardíacos / Transplante de Células-Tronco / Nanopartículas / Células-Tronco Pluripotentes Induzidas / Plásticos Biodegradáveis / Cardiopatias Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Miócitos Cardíacos / Transplante de Células-Tronco / Nanopartículas / Células-Tronco Pluripotentes Induzidas / Plásticos Biodegradáveis / Cardiopatias Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article