Modelling human skin: organotypic cultures for applications in toxicology, immunity, and cancer

ABSTRATC: Animal models are important tools to better understand different skin processes. These are widely used for chemical hazard identification and to study skin-related pathologies. Despite the complexity they offer, animal skin is not a perfect model of human skin. This and the growing ethical...

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Autores:
Gaviria Agudelo, Catalina
Tipo de recurso:
Doctoral thesis
Fecha de publicación:
2021
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/24435
Acceso en línea:
http://hdl.handle.net/10495/24435
Palabra clave:
Neoplasias cutáneas
Fibrina
Enfermedades de la piel
Ingeniería de tejidos
Modelos biológicos
Materiales biocompatibles
Bioingeniería
Skin neoplasms
Fibrin
Skin diseases
Models, biological
Biocompatible materials
Bioengineering
http://id.nlm.nih.gov/mesh/D012878
http://id.nlm.nih.gov/mesh/D005337
http://id.nlm.nih.gov/mesh/D012871
http://id.nlm.nih.gov/mesh/D008954
http://id.nlm.nih.gov/mesh/D001672
http://id.nlm.nih.gov/mesh/D057005
Rights
embargoedAccess
License
http://creativecommons.org/licenses/by-nc-sa/2.5/co/
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oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/24435
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dc.title.spa.fl_str_mv Modelling human skin: organotypic cultures for applications in toxicology, immunity, and cancer
title Modelling human skin: organotypic cultures for applications in toxicology, immunity, and cancer
spellingShingle Modelling human skin: organotypic cultures for applications in toxicology, immunity, and cancer
Neoplasias cutáneas
Fibrina
Enfermedades de la piel
Ingeniería de tejidos
Modelos biológicos
Materiales biocompatibles
Bioingeniería
Skin neoplasms
Fibrin
Skin diseases
Models, biological
Biocompatible materials
Bioengineering
http://id.nlm.nih.gov/mesh/D012878
http://id.nlm.nih.gov/mesh/D005337
http://id.nlm.nih.gov/mesh/D012871
http://id.nlm.nih.gov/mesh/D008954
http://id.nlm.nih.gov/mesh/D001672
http://id.nlm.nih.gov/mesh/D057005
title_short Modelling human skin: organotypic cultures for applications in toxicology, immunity, and cancer
title_full Modelling human skin: organotypic cultures for applications in toxicology, immunity, and cancer
title_fullStr Modelling human skin: organotypic cultures for applications in toxicology, immunity, and cancer
title_full_unstemmed Modelling human skin: organotypic cultures for applications in toxicology, immunity, and cancer
title_sort Modelling human skin: organotypic cultures for applications in toxicology, immunity, and cancer
dc.creator.fl_str_mv Gaviria Agudelo, Catalina
dc.contributor.advisor.none.fl_str_mv Restrepo Múnera, Luz Marina
Foijer, Floris
dc.contributor.author.none.fl_str_mv Gaviria Agudelo, Catalina
dc.subject.mesh.none.fl_str_mv Neoplasias cutáneas
Fibrina
Enfermedades de la piel
Ingeniería de tejidos
Modelos biológicos
Materiales biocompatibles
Bioingeniería
Skin neoplasms
Fibrin
Skin diseases
Models, biological
Biocompatible materials
Bioengineering
topic Neoplasias cutáneas
Fibrina
Enfermedades de la piel
Ingeniería de tejidos
Modelos biológicos
Materiales biocompatibles
Bioingeniería
Skin neoplasms
Fibrin
Skin diseases
Models, biological
Biocompatible materials
Bioengineering
http://id.nlm.nih.gov/mesh/D012878
http://id.nlm.nih.gov/mesh/D005337
http://id.nlm.nih.gov/mesh/D012871
http://id.nlm.nih.gov/mesh/D008954
http://id.nlm.nih.gov/mesh/D001672
http://id.nlm.nih.gov/mesh/D057005
dc.subject.meshuri.none.fl_str_mv http://id.nlm.nih.gov/mesh/D012878
http://id.nlm.nih.gov/mesh/D005337
http://id.nlm.nih.gov/mesh/D012871
http://id.nlm.nih.gov/mesh/D008954
http://id.nlm.nih.gov/mesh/D001672
http://id.nlm.nih.gov/mesh/D057005
description ABSTRATC: Animal models are important tools to better understand different skin processes. These are widely used for chemical hazard identification and to study skin-related pathologies. Despite the complexity they offer, animal skin is not a perfect model of human skin. This and the growing ethical concern about animal experimentation has led to the development of alternative methods that are in line with the 3 rules guidelines (reduction, refinement and replacement of animals in experiments) within the seventh amendment to the EU Cosmetics Directive 76/768/EEC. One of these alternatives are human skin explant models. Such models contain the main cellular components, a skin barrier function, and a mature stratum corneum, and are therefore highly suitable to replace animal testing. However, they rely on a regular supply of fresh tumor biopsies of proper size, limiting their use in drug testing assays. Another alternative, in vitro bi-dimensional (2D) skin models, have been produced as well, but they are restricted by the lack of similarity to the skin in vivo structure, phenotype, and behavior. Therefore, three-dimensional (3D) skin substitutes represent a powerful alternative to animal testing. Over the last years, many elegant studies have developed 3D models composed of human skin cells and extracellular matrix components. Still, most of them are limited to one cellular type, neglecting the contribution of other important elements like the dermis, the immune component, or interaction between different cell types. Therefore, to better understand skin behavior and responses, models that more faithfully mimic the human skin are needed. In this thesis, we aimed to develop 3D fibrin-based human skin equivalents for applications in the fields of toxicology, immunology, and cancer, containing both the dermal and epidermal compartments.
publishDate 2021
dc.date.accessioned.none.fl_str_mv 2021-11-29T19:39:02Z
dc.date.available.none.fl_str_mv 2021-11-29T19:39:02Z
dc.date.issued.none.fl_str_mv 2021
dc.type.spa.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/TD
dc.type.local.spa.fl_str_mv Tesis/Trabajo de grado - Monografía - Doctorado
format http://purl.org/coar/resource_type/c_db06
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dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/10495/24435
url http://hdl.handle.net/10495/24435
dc.language.iso.spa.fl_str_mv eng
language eng
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dc.format.extent.spa.fl_str_mv 141
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dc.publisher.place.spa.fl_str_mv Medellín
institution Universidad de Antioquia
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repository.name.fl_str_mv Repositorio Institucional Universidad de Antioquia
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spelling Restrepo Múnera, Luz MarinaFoijer, FlorisGaviria Agudelo, Catalina2021-11-29T19:39:02Z2021-11-29T19:39:02Z2021http://hdl.handle.net/10495/24435ABSTRATC: Animal models are important tools to better understand different skin processes. These are widely used for chemical hazard identification and to study skin-related pathologies. Despite the complexity they offer, animal skin is not a perfect model of human skin. This and the growing ethical concern about animal experimentation has led to the development of alternative methods that are in line with the 3 rules guidelines (reduction, refinement and replacement of animals in experiments) within the seventh amendment to the EU Cosmetics Directive 76/768/EEC. One of these alternatives are human skin explant models. Such models contain the main cellular components, a skin barrier function, and a mature stratum corneum, and are therefore highly suitable to replace animal testing. However, they rely on a regular supply of fresh tumor biopsies of proper size, limiting their use in drug testing assays. Another alternative, in vitro bi-dimensional (2D) skin models, have been produced as well, but they are restricted by the lack of similarity to the skin in vivo structure, phenotype, and behavior. Therefore, three-dimensional (3D) skin substitutes represent a powerful alternative to animal testing. Over the last years, many elegant studies have developed 3D models composed of human skin cells and extracellular matrix components. Still, most of them are limited to one cellular type, neglecting the contribution of other important elements like the dermis, the immune component, or interaction between different cell types. Therefore, to better understand skin behavior and responses, models that more faithfully mimic the human skin are needed. In this thesis, we aimed to develop 3D fibrin-based human skin equivalents for applications in the fields of toxicology, immunology, and cancer, containing both the dermal and epidermal compartments.RESUMEN: Los modelos animales son herramientas importantes para el estudio de la biología de la piel humana y los mecanismos subyacentes. A pesar de la complejidad que ofrecen y de ser ampliamente utilizados para estimar el riesgo potencial de sustancias químicas e investigar diferentes patologías cutáneas, no son modelos perfectos de piel humana. Esto y la creciente preocupación ética por la experimentación animal ha dado lugar al desarrollo de métodos alternativos que estén en línea con el principio de las 3R (reducción, refinamiento y reemplazo de animales de laboratorio) dentro de la séptima enmienda a la Directiva de Cosméticos de la UE 76/768/EEC. Los explantes de piel humana contienen los principales componentes celulares, conservan la función barrera de la piel y presentan un estrato córneo maduro, por lo que son altamente adecuados como reemplazo de pruebas con animales. Sin embargo, tienen como principal desventaja la necesidad de contar con un suministro constante de biopsias frescas de tamaño adecuado, lo que limita su uso en pruebas de toxicidad. Asimismo, se han producido varios modelos de piel in vitro bidimensionales (2D) que sin embargo, están limitados por la falta de similitud con la estructura, fenotipo y función de la piel nativa. Por otro lado, los modelos de piel tridimensionales (3D) representan una poderosa alternativa contra la experimentación animal. En los últimos años, diferentes estudios se han enfocado en el desarrollo de sustitutos 3D compuestos por células de piel humana y productos de la matriz extracelular. No obstante, la mayoría sólo incluye un tipo celular, pasando por alto la contribución de elementos importantes como la dermis, el componente inmunológico o la interacción entre diferentes tipos de células. Por lo tanto, para un mejor estudio de la piel y sus respuestas, se necesitan modelos que imiten más fielmente la piel humana. En esta tesis, nos enfocamos en el desarrollo de modelos dermo-epidérmicos 3D de piel humana para aplicaciones en el campo de la toxicología, la inmunología y el cáncer, utilizando como soporte un scaffold de fibrina.TESIS CON DISTINCIÓN: Cum Laude141application/pdfenginfo:eu-repo/semantics/draftinfo:eu-repo/semantics/doctoralThesishttp://purl.org/coar/resource_type/c_db06https://purl.org/redcol/resource_type/TDTesis/Trabajo de grado - Monografía - Doctoradohttp://purl.org/coar/version/c_b1a7d7d4d402bcceinfo:eu-repo/semantics/embargoedAccesshttp://creativecommons.org/licenses/by-nc-sa/2.5/co/http://purl.org/coar/access_right/c_f1cfhttps://creativecommons.org/licenses/by-nc-sa/4.0/Neoplasias cutáneasFibrinaEnfermedades de la pielIngeniería de tejidosModelos biológicosMateriales biocompatiblesBioingenieríaSkin neoplasmsFibrinSkin diseasesModels, biologicalBiocompatible materialsBioengineeringhttp://id.nlm.nih.gov/mesh/D012878http://id.nlm.nih.gov/mesh/D005337http://id.nlm.nih.gov/mesh/D012871http://id.nlm.nih.gov/mesh/D008954http://id.nlm.nih.gov/mesh/D001672http://id.nlm.nih.gov/mesh/D057005Modelling human skin: organotypic cultures for applications in toxicology, immunity, and cancerMedellínDoctora en Ciencias Básicas BiomédicasDoctoradoCorporación Académica Ciencias Básicas Biomédicas. Doctorado en Ciencias Básicas BiomédicasUniversidad de AntioquiaORIGINALGaviriaCatalina_2021_ModellingHumanSkin.pdfGaviriaCatalina_2021_ModellingHumanSkin.pdfTesis doctoralapplication/pdf4849356https://bibliotecadigital.udea.edu.co/bitstream/10495/24435/1/GaviriaCatalina_2021_ModellingHumanSkin.pdf0ffc7639e4c2b5699ba8b21d9e4fbe1cMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-81051https://bibliotecadigital.udea.edu.co/bitstream/10495/24435/5/license_rdfe2060682c9c70d4d30c83c51448f4eedMD55LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstream/10495/24435/6/license.txt8a4605be74aa9ea9d79846c1fba20a33MD5610495/24435oai:bibliotecadigital.udea.edu.co:10495/244352022-08-02 10:16:34.128Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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