Amaro Prellezo, Elena

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    Topical Administration of a Marine Oil Rich in Pro-Resolving Lipid Mediators Accelerates Wound Healing in Diabetic db/db Mice through Angiogenesis and Macrophage Polarization
    (MDPI AG, 2022-08-31) Amaro Prellezo, Elena; Ontoria-Oviedo, Imelda; Castellano, Delia; Venegas-Venegas, Elena; González-Santos, Fernando; Ruiz-Saurí, Amparo; Pelacho, Beatriz; Prósper, Felipe; Pérez del Caz, María Dolores; Sepúlveda, Pilar; Centro de Biomateriales e Ingeniería Tisular; Instituto de Salud Carlos III; European Regional Development Fund; Ministerio de Economía y Competitividad; Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana
    [EN] Impaired wound healing in patients with type 2 diabetes (DM2) is characterized by chronic inflammation, which delays wound closure. Specialized pro-resolving lipid mediators (SPMs) are bioactive molecules produced from essential polyunsaturated fatty acids (PUFAs), principally omega-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). SPMs are potent regulators of inflammation and have been used to suppress chronic inflammation in peripheral artery disease, non-alcoholic fatty liver disease, and central nervous system syndromes. LIPINOVA® is a commercially available safe-grade nutritional supplement made from a fractionated marine lipid concentrate derived from anchovy and sardine oil that is rich in SPMs and EPA, as well as DHA precursors. Here, we assessed the effect of LIPINOVA® in wound dressing applications. LIPINOVA® showed biocompatibility with keratinocytes and fibroblasts, reduced the abundance of pro-inflammatory macrophages (M¿1), and promoted in vitro wound closure. Daily application of the marine oil to open wounds made by punch biopsy in db/db mice promoted wound closure by accelerating the resolution of inflammation, inducing neoangiogenesis and M¿1/M¿2 macrophage polarization. In conclusion, LIPINOVA® displays pro-resolutive properties and could be exploited as a therapeutic agent for the treatment of diabetic ulcers.
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    Extracellular vesicles from dental pulp mesenchymal stem cells modulate macrophage phenotype during acute and chronic cardiac inflammation in athymic nude rats with myocardial infarction
    (2024-05-28) Amaro Prellezo, Elena; Gómez-Ferrer, Marta; Hakobyan, Lusine; Ontoria-Oviedo, Imelda; Peiró-Molina, Esteban; Tarazona Campos, Sonia; Salguero, Pedro; Ruiz-Saurí, Amparo; Selva-Roldán, Marta; Vives-Sanchez, Rosa; Sepúlveda, Pilar; Departamento de Estadística e Investigación Operativa Aplicadas y Calidad; Centro de Biomateriales e Ingeniería Tisular; Escuela Técnica Superior de Ingeniería Informática; Grupo de Ingeniería Estadística Multivariante GIEM; Generalitat Valenciana; Ministerio de Universidades; Instituto de Salud Carlos III; European Regional Development Fund; Agència Valenciana de la Innovació; Ministerio de Economía y Competitividad; Instituto de Investigación Sanitaria La Fe; Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana
    [EN] Background/aims Extracellular vesicles (EVs) derived from dental pulp mesenchymal stem cells (DP-MSCs) are a promising therapeutic option for the treatment of myocardial ischemia. The aim of this study is to determine whether MSC-EVs could promote a pro-resolving environment in the heart by modulating macrophage populations.Methods EVs derived from three independent biopsies of DP-MSCs (MSC-EVs) were isolated by tangential flow-filtration and size exclusion chromatography and were characterized by omics analyses. Biological processes associated with these molecules were analyzed using String and GeneCodis platforms. The immunomodulatory capacity of MSC-EVs to polarize macrophages towards a pro-resolving or M2-like phenotype was assessed by evaluating surface markers, cytokine production, and efferocytosis. The therapeutic potential of MSC-EVs was evaluated in an acute myocardial infarction (AMI) model in nude rats. Infarct size and the distribution of macrophage populations in the infarct area were evaluated 7 and 21 days after intramyocardial injection of MSC-EVs.Results Lipidomic, proteomic, and miRNA-seq analysis of MSC-EVs revealed their association with biological processes involved in tissue regeneration and regulation of the immune system, among others. MSC-EVs promoted the differentiation of pro-inflammatory macrophages towards a pro-resolving phenotype, as evidenced by increased expression of M2 markers and decreased secretion of pro-inflammatory cytokines. Administration of MSC-EVs in rats with AMI limited the extent of the infarcted area at 7 and 21 days post-infarction. MSC-EV treatment also reduced the number of pro-inflammatory macrophages within the infarct area, promoting the resolution of inflammation.Conclusion EVs derived from DP-MSCs exhibited similar characteristics at the omics level irrespective of the biopsy from which they were derived. All MSC-EVs exerted effective pro-resolving responses in a rat model of AMI, indicating their potential as therapeutic agents for the treatment of inflammation associated with AMI.