Editorial
Do Experimental COPD Models Make Sense?
Modelos experimentales de EPOC. ¿Tienen sentido?
Servicio de Neumología, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, CIBERES, Madrid, Spain
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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "65" "paginaFinal" => "66" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Sandra Pérez-Rial, Germán Peces-Barba" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Sandra" "apellidos" => "Pérez-Rial" ] 1 => array:4 [ "nombre" => "Germán" "apellidos" => "Peces-Barba" "email" => array:1 [ 0 => "gpeces@fjd.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Neumología, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, CIBERES, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Modelos experimentales de EPOC. ¿Tienen sentido?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The use of animal models of a disease usually progresses in parallel with research carried out on that disease, and generally follows 2 main lines: anticipating the value of a particular gene or biological marker and subsequently transferring this to the patient; or using animal models as a platform for an in-depth analysis of the pathways involved in a marker that was first detected in patients.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In COPD, most commonly used model is the murine model of exposure to tobacco smoke.</p><p id="par0015" class="elsevierStylePara elsevierViewall">This model admittedly has some limitations, such as the absence of ciliated cells and goblet cells characteristic of the human bronchial epithelium in the murine bronchial epithelium, and its inability to model disease progression after stopping smoking. Nevertheless, it is a very versatile technique that offers multiple combinations. For example, pathological production of mucus can be achieved by combining the endobronchial administration of bacterial lipopolysaccharides (LPS) with exposure to tobacco smoke.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> Other aspects of its versatility are the availability of a wide catalog of mutational variants, relatively easy access to specific antibodies, and lower costs than in other species. In short, experimental intervention in the regulation of molecular pathways is more accessible.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Many of the characteristics of COPD can be reproduced in animal models, including pulmonary emphysema and remodeling of the airways and pulmonary vessels.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> Exacerbation models can also be reproduced by inducing viral or bacterial infections<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> or by administering toxins such as LPS.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> Models can even be used to study associated systemic involvement, for example, in the muscles and skeleton.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> The conventional patterns of exposure to tobacco smoke can only achieve mild-moderate disease intensities, but greater severity can be induced with the associated use of other toxic agents, such as intratracheal cadmium chloride or elastase<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> or with the use of especially sensitive mutants.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> This versatility enables the design of targeted experiments to answer specific research questions. When a new hypothesis is being explored, animal models are the researcher's first choice due to their advantages over cell-based assays or tests performed directly in humans. However, the animal model must be carefully selected, depending on the disease characteristic to be examined or treated. The induced onset and progression of COPD are highly influenced by a complex interaction between the immune system and the mechanical properties of the lung tissue that cause chronic inflammation and tissue remodeling. Therefore, a model designed, let us say, for the study of a pathogenic metabolic pathway that participates in the onset of the disease will not be suitable for a therapeutic trial examining the advanced stages.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The use of models of chronic exposure to cigarette smoke increased after it was established that morphological and physiological manifestations of emphysema could be found, first in guinea pigs<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> and later in mice.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> This exposure increases lung inflammation, protease activity, oxidative stress, and apoptosis, and in selected strains leads to the development of moderate emphysema and mild grades of small airway remodeling, with deterioration of lung function, vascular remodeling, and pulmonary hypertension.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,10</span></a> Practically all possible features of COPD in patients can be found in the models.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Lung development and maturation differ among the different animal species, as does lung anatomy. Even within a given species, there is a marked variation between the different strains, with widely varying susceptibility and response to the injury-inducing agents. This means that individual susceptibilities to developing the disease among smokers can be investigated, although a finding in an animal model of COPD cannot always be transferred to patients. Many studies are looking for common genes and pathways that might help explain the differences in susceptibility or resistance to the development of COPD.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> In the referenced study, different mouse strains, both susceptible and resistant to emphysema (transgenic and wild strains), were exposed to cigarette smoke for a period of 6 months during which gene expression in the entire lung was analyzed, and the results were compared with gene expression studies in the lungs of non-smokers and former smokers, with or without COPD. More differences than similarities were found when all pulmonary gene expression profiles were compared, both within the same mouse species, and when the results were compared with the expression profiles of patients with COPD. These findings show that responses in gene expression to cigarette smoke are largely species- and model-dependent, but certain shared pathways can provide significant understanding of the biology that underlies individual susceptibility to exposure to cigarette smoke. Understanding these differences is important if therapeutic targets in COPD are to be translated from mouse studies to humans.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In addition to serving as a basis for research into metabolic targets, COPD models can also assist in the study of phenotypic variants of the disease, which are emerging as new platforms for study. For example, the combined administration of ovalbumin and tobacco smoke can induce mixed COPD/asthma, permitting analysis of the metabolic interactions characteristic of this presentation.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Thanks to the use of the models, new therapeutic targets can be identified, and a multitude of experimental tests can be performed that would otherwise be impossible. We have evidence of regenerative therapy using mesenchymal cells,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> growth factors,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> and other commercial compounds.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> Virtually all new treatments need a preclinical phase of animal experimentation before they can be applied to patients.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In short, experimental models continue to provide quality information on complex, interconnected immune pathways and continue to be essential for unraveling the role of those myriad genes whose action remains to be clarified, and, incidentally, for verifying the similarities of gene functions between humans and mice, the sword of Damocles of animal research.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Pérez-Rial S, Peces-Barba G. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 41 | 17 | 58 |
| 2024 September | 43 | 18 | 61 |
| 2024 August | 64 | 44 | 108 |
| 2024 July | 43 | 21 | 64 |
| 2024 June | 56 | 32 | 88 |
| 2024 May | 74 | 31 | 105 |
| 2024 April | 26 | 35 | 61 |
| 2024 March | 37 | 19 | 56 |
| 2024 February | 30 | 18 | 48 |
| 2023 March | 10 | 4 | 14 |
| 2023 February | 50 | 20 | 70 |
| 2023 January | 22 | 44 | 66 |
| 2022 December | 41 | 35 | 76 |
| 2022 November | 45 | 19 | 64 |
| 2022 October | 50 | 31 | 81 |
| 2022 September | 22 | 16 | 38 |
| 2022 August | 29 | 47 | 76 |
| 2022 July | 24 | 31 | 55 |
| 2022 June | 25 | 31 | 56 |
| 2022 May | 24 | 35 | 59 |
| 2022 April | 29 | 31 | 60 |
| 2022 March | 55 | 41 | 96 |
| 2022 February | 30 | 36 | 66 |
| 2022 January | 20 | 35 | 55 |
| 2021 December | 33 | 31 | 64 |
| 2021 November | 54 | 31 | 85 |
| 2021 October | 65 | 45 | 110 |
| 2021 September | 32 | 39 | 71 |
| 2021 August | 40 | 34 | 74 |
| 2021 July | 19 | 17 | 36 |
| 2021 June | 40 | 33 | 73 |
| 2021 May | 51 | 36 | 87 |
| 2021 April | 76 | 90 | 166 |
| 2021 March | 38 | 28 | 66 |
| 2021 February | 22 | 15 | 37 |
| 2020 March | 8 | 3 | 11 |
| 2020 February | 17 | 15 | 32 |
| 2020 January | 23 | 12 | 35 |
| 2019 December | 25 | 12 | 37 |
| 2019 November | 18 | 14 | 32 |
| 2019 October | 27 | 11 | 38 |
| 2019 September | 15 | 2 | 17 |
| 2019 August | 24 | 9 | 33 |
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