Amaro Prellezo, Elena
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- PublicationTopical 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-SaurÃ, Amparo; Pelacho, Beatriz; Prósper, Felipe; Pérez del Caz, MarÃa Dolores; Sepúlveda, Pilar; Centro de Biomateriales e IngenierÃa Tisular; Instituto de Salud Carlos III; European Regional Development Fund; Ministerio de EconomÃa 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.
- PublicationExtracellular 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-SaurÃ, Amparo; Selva-Roldán, Marta; Vives-Sanchez, Rosa; Sepúlveda, Pilar; Departamento de EstadÃstica e Investigación Operativa Aplicadas y Calidad; Centro de Biomateriales e IngenierÃa Tisular; Escuela Técnica Superior de IngenierÃa Informática; Grupo de IngenierÃa EstadÃstica Multivariante GIEM; Generalitat Valenciana; Ministerio de Universidades; Instituto de Salud Carlos III; European Regional Development Fund; Agència Valenciana de la Innovació; Ministerio de EconomÃa 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.
- PublicationConductive polycaprolactone/gelatin/polyaniline nanofibres as functional scaffolds for cardiac tissue regeneration(Elsevier, 2022-01) Gil-Castell, O.; Ontoria-Oviedo, I.; Badia, J.D.; Amaro Prellezo, Elena; Sepúlveda, P.; Ribes Greus, MarÃa Desamparados; Departamento de Máquinas y Motores Térmicos; Centro de Biomateriales e IngenierÃa Tisular; Escuela Técnica Superior de IngenierÃa Industrial; Instituto Universitario de Investigación de TecnologÃa de los Materiales de la UPV; GENERALITAT VALENCIANA; European Regional Development Fund; Universitat Politècnica de València; Ministerio de EconomÃa y Competitividad; Centro de Investigación PrÃncipe Felipe; Instituto de Investigación Sanitaria La Fe; Centre for Forestry Research and Experimentation[EN] The endorsement of functional features such as biocompatibility, mechanical integrity, or electrical conductivity to tissue engineering (TE) scaffolds is essential to stimulate cell adhesion and proliferation. In this study, electrospun nanofibers based on polycaprolactone (PCL) and gelatin (Ge) (ratios 60/40, 50/50, and 40/60), and polyaniline (PAni) particles (0.25, 0.50, and 1.00 %wt) were prepared. The time of dissolution in an acid solvent mixture before electrospinning allowed for obtaining nanofibers with controlled features. Changes in the molar mass (Mn from 90·103 to 15·103 g·mol-1), in the crystalline microstructure (Xc from 60 to 25%) and the surface morphology (diameter from 250 to 50 nm) due to the controlled hydrolytic action on PCL were found. In vitro degradability and biocompatibility were favoured as the dissolution time and gelatin percentage increased. The presence of PAni was revealed as non-cytotoxic and promoted a controlled increase of the electrical conductivity, that contributed to in vitro cardiomyocyte proliferation. Cellular centres in the vicinities of PAni microparticles could be identified in the scaffold with the 40/60 PCL/Ge scaffold with PAni (1.00 %wt), keeping the macrophages profile unaltered, which may determine the satisfactory resolution of cardiac injury and point out these scaffolds as appropriate candidates for cardiac TE.