Publicaciones científicas

Interacting resident epicardium-derived fibroblasts and recruited bone marrow cells form myocardial infarction scar

Ruiz-Villalba A(1), Simón AM(2), Pogontke C(3), Castillo MI(3), Abizanda G(2), Pelacho B(4), Sánchez-Domínguez R(5), Segovia JC(5), Prósper F(2), Pérez-Pomares JM(6).

(1) Department of Animal Biology, Faculty of Sciences, University of Málaga, Málaga, Spain; Department of Anatomy, Embryology and Physiology, AMC-University of Amsterdam, Amsterdam, the Netherlands.
(2) Department of Hematology, Clínica Universitaria de Navarra-CIMA, Universidad de Navarra, Pamplona, Spain.
(3) Department of Animal Biology, Faculty of Sciences, University of Málaga, Málaga, Spain; Andalusian Center for Nanomedicine and Biotechnology, Campanillas (Málaga), Spain.
(4) Stem Cell Therapy Area, Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
(5) Differentiation and Cytometry Unit, Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas-Centro de Investigaciones Biomédicas en Red de Enfermedades Raras, Madrid, Spain; Advanced Therapies Mixed Unit, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain.
(6) Department of Animal Biology, Faculty of Sciences, University of Málaga, Málaga, Spain; Andalusian Center for Nanomedicine and Biotechnology, Campanillas (Málaga), Spain.

Revista: Journal of the American College of Cardiology

Fecha: 19-may-2015

Área de Terapia Celular

BACKGROUND:
Although efforts continue to find new therapies to regenerate infarcted heart tissue, knowledge of the cellular and molecular mechanisms involved remains poor. 

OBJECTIVES:
This study sought to identify the origin of cardiac fibroblasts (CFs) in the infarcted heart to better understand the pathophysiology of ventricular remodeling following myocardial infarction (MI). 

METHODS:
Permanent genetic tracing of epicardium-derived cell (EPDC) and bone marrow-derived blood cell (BMC) lineages was established using Cre/LoxP technology. In vivo gene and protein expression studies, as well as in vitro cell culture assays, were developed to characterize EPDC and BMC interaction and properties. 

RESULTS:
EPDCs, which colonize the cardiac interstitium during embryogenesis, massively differentiate into CFs after MI. This response is disease-specific, because angiotensin II-induced pressure overload does not trigger significant EPDC fibroblastic differentiation. The expansion of epicardial-derived CFs follows BMC infiltration into the infarct site; the number of EPDCs equals that of BMCs 1 week post-infarction. BMC-EPDC interaction leads to cell polarization, packing, massive collagen deposition, and scar formation. Moreover, epicardium-derived CFs display stromal properties with respect to BMCs, contributing to the sustained recruitment of circulating cells to the damaged zone and the cardiac persistence of hematopoietic progenitors/stem cells after MI. 

CONCLUSIONS:
EPDCs, but not BMCs, are the main origin of CFs in the ischemic heart. Adult resident EPDC contribution to the CF compartment is time- and disease-dependent. Our findings are relevant to the understanding of post-MI ventricular remodeling and may contribute to the development of new therapies to treat this disease.

CITA DEL ARTÍCULO  J Am Coll Cardiol. 2015 May 19;65(19):2057-66. doi: 10.1016/j.jacc.2015.03.520.

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