Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones
[EN] Background: Extracellular histones (extH) have emerged as key damage-associated molecular patterns (DAMPs) driving multi-organ failure in sepsis. Despite their correlation with disease severity, organ-specific mechanisms of extH toxicity and targeted therapeutic strategies remain underexplored....
| Autores: | , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2026 |
| País: | España |
| Institución: | Universitat Politècnica de València (UPV) |
| Repositorio: | RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia |
| Idioma: | inglés |
| OAI Identifier: | oai:dnet:riunet______::7849b6fb394375db0e9cc5746652b848 |
| Acceso en línea: | https://riunet.upv.es/handle/10251/235575 |
| Access Level: | acceso abierto |
| Palabra clave: | Sepsis Extracellular histones Organoids 3D biomodels Organ-on-chip Bioprinting |
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Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones |
| title |
Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones |
| spellingShingle |
Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones Garcia-Gimenez, Jose Luis Sepsis Extracellular histones Organoids 3D biomodels Organ-on-chip Bioprinting |
| title_short |
Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones |
| title_full |
Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones |
| title_fullStr |
Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones |
| title_full_unstemmed |
Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones |
| title_sort |
Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones |
| dc.creator.none.fl_str_mv |
Garcia-Gimenez, Jose Luis Cervera, Marta Seco Canovas-Cervera, Irene Agundez, Ana Belen Dolz-Andres, Enric Mondaray-Munoz, Gonzalo Calpe-Fortea, Rosa Nacher-Sendra, Elena Osca-Verdegal, Rebeca Beltran-Garcia, Jesus Sierra-Rivera, Antonio Peiro-Chova, Lorena Ibañez-Cabellos, J.S. Aparicio-Collado, José Luís|||0000-0003-0874-9131 Gallego-Ferrer, Gloria|||0000-0002-2428-0903 |
| author |
Garcia-Gimenez, Jose Luis |
| author_facet |
Garcia-Gimenez, Jose Luis Cervera, Marta Seco Canovas-Cervera, Irene Agundez, Ana Belen Dolz-Andres, Enric Mondaray-Munoz, Gonzalo Calpe-Fortea, Rosa Nacher-Sendra, Elena Osca-Verdegal, Rebeca Beltran-Garcia, Jesus Sierra-Rivera, Antonio Peiro-Chova, Lorena Ibañez-Cabellos, J.S. Aparicio-Collado, José Luís|||0000-0003-0874-9131 Gallego-Ferrer, Gloria|||0000-0002-2428-0903 |
| author_role |
author |
| author2 |
Cervera, Marta Seco Canovas-Cervera, Irene Agundez, Ana Belen Dolz-Andres, Enric Mondaray-Munoz, Gonzalo Calpe-Fortea, Rosa Nacher-Sendra, Elena Osca-Verdegal, Rebeca Beltran-Garcia, Jesus Sierra-Rivera, Antonio Peiro-Chova, Lorena Ibañez-Cabellos, J.S. Aparicio-Collado, José Luís|||0000-0003-0874-9131 Gallego-Ferrer, Gloria|||0000-0002-2428-0903 |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Termodinámica Aplicada Centro de Biomateriales e Ingeniería Tisular Escuela Técnica Superior de Ingeniería Industrial Generalitat Valenciana Instituto de Salud Carlos III Agencia Estatal de Investigación Ministerio de Ciencia, Innovación y Universidades Repositorio Institucional de la Universitat Politècnica de València Riunet |
| dc.subject.none.fl_str_mv |
Sepsis Extracellular histones Organoids 3D biomodels Organ-on-chip Bioprinting |
| topic |
Sepsis Extracellular histones Organoids 3D biomodels Organ-on-chip Bioprinting |
| description |
[EN] Background: Extracellular histones (extH) have emerged as key damage-associated molecular patterns (DAMPs) driving multi-organ failure in sepsis. Despite their correlation with disease severity, organ-specific mechanisms of extH toxicity and targeted therapeutic strategies remain underexplored. Main body: This review dissects extH-mediated pathophysiology across vital organs including heart, lungs, kidneys, liver, and brain, through convergent pathways including TLR activation, NLRP3 inflammasome signaling, NETosis, oxidative stress, calcium influx, pyroptosis, and microvascular thrombosis. Conventional 2D cell cultures fail to recapitulate tissue architecture, multicellular interactions, and hemodynamic forces, while rodent models exhibit poor clinical translatability due to specific immune responses and physiology. Moreover, conventional 2D models and animal models do not usually cover the heterogenicity we can find in sepsis. In contrast, advanced human-relevant 3D biomodels offer transformative advantages: organoids faithfully recreate organ-specific cellular heterogeneity and developmental gradients; 3D-bioprinted biomodels provide precise spatial control of immune-endothelial-stromal interactions within biomimetic matrices; organ-on-chip platforms integrate physiological shear stress, dynamic flow, oxygen gradients, and real-time inter-organ communication, enabling study of extH-driven neutrophil adhesion, platelet aggregation, barrier dysfunction, and cytokine storms under clinically relevant conditions. Conclusion: Next-generation 3D biomodels overcome traditional translational barriers, facilitating the comprehension of the pathophysiological mechanisms occurring in tissues during sepsis. Moreover, these advanced biomodels enable high-throughput screening of extH-neutralizing agents (e.g., heparinoids, anti-histone antibodies) and hemoperfusion technologies, thereby advancing precision intensive care medicine. By bridging mechanistic insights to clinical strategies that mitigate inflammation, endothelial dysfunction, thrombosis and long-term sequelae, these platforms promise transformative advances in sepsis management and intensive care outcomes. |
| publishDate |
2026 |
| dc.date.none.fl_str_mv |
2026 2026-06-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://riunet.upv.es/handle/10251/235575 |
| url |
https://riunet.upv.es/handle/10251/235575 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Generalitat Valenciana https://doi.org/10.13039/501100003359 CIAICO%2F2023%2F168 Generalitat Valenciana https://doi.org/10.13039/501100003359 CIAPOT%2F2024%2F19 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI22-00481 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI25-00664 Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 CPP2021%2F008643 Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 FPU23%2F02919 Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 DTS24%2F00094 Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 PTQ2024-013788 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Reconocimiento - No comercial (by-nc) http://creativecommons.org/licenses/by-nc/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 Reconocimiento - No comercial (by-nc) http://creativecommons.org/licenses/by-nc/4.0/ |
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openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia instname:Universitat Politècnica de València (UPV) |
| instname_str |
Universitat Politècnica de València (UPV) |
| reponame_str |
RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia |
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RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia |
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1869409686213623808 |
| spelling |
Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histonesGarcia-Gimenez, Jose LuisCervera, Marta SecoCanovas-Cervera, IreneAgundez, Ana BelenDolz-Andres, EnricMondaray-Munoz, GonzaloCalpe-Fortea, RosaNacher-Sendra, ElenaOsca-Verdegal, RebecaBeltran-Garcia, JesusSierra-Rivera, AntonioPeiro-Chova, LorenaIbañez-Cabellos, J.S.Aparicio-Collado, José Luís|||0000-0003-0874-9131Gallego-Ferrer, Gloria|||0000-0002-2428-0903SepsisExtracellular histonesOrganoids3D biomodelsOrgan-on-chipBioprinting[EN] Background: Extracellular histones (extH) have emerged as key damage-associated molecular patterns (DAMPs) driving multi-organ failure in sepsis. Despite their correlation with disease severity, organ-specific mechanisms of extH toxicity and targeted therapeutic strategies remain underexplored. Main body: This review dissects extH-mediated pathophysiology across vital organs including heart, lungs, kidneys, liver, and brain, through convergent pathways including TLR activation, NLRP3 inflammasome signaling, NETosis, oxidative stress, calcium influx, pyroptosis, and microvascular thrombosis. Conventional 2D cell cultures fail to recapitulate tissue architecture, multicellular interactions, and hemodynamic forces, while rodent models exhibit poor clinical translatability due to specific immune responses and physiology. Moreover, conventional 2D models and animal models do not usually cover the heterogenicity we can find in sepsis. In contrast, advanced human-relevant 3D biomodels offer transformative advantages: organoids faithfully recreate organ-specific cellular heterogeneity and developmental gradients; 3D-bioprinted biomodels provide precise spatial control of immune-endothelial-stromal interactions within biomimetic matrices; organ-on-chip platforms integrate physiological shear stress, dynamic flow, oxygen gradients, and real-time inter-organ communication, enabling study of extH-driven neutrophil adhesion, platelet aggregation, barrier dysfunction, and cytokine storms under clinically relevant conditions. Conclusion: Next-generation 3D biomodels overcome traditional translational barriers, facilitating the comprehension of the pathophysiological mechanisms occurring in tissues during sepsis. Moreover, these advanced biomodels enable high-throughput screening of extH-neutralizing agents (e.g., heparinoids, anti-histone antibodies) and hemoperfusion technologies, thereby advancing precision intensive care medicine. By bridging mechanistic insights to clinical strategies that mitigate inflammation, endothelial dysfunction, thrombosis and long-term sequelae, these platforms promise transformative advances in sepsis management and intensive care outcomes.We would like to thank all the funding bodies supporting our research projects, including the EIC Accelerator programme, supported by CDTI - NextGenerationEU (Ministerio de Ciencia, Innovacion y Universidades) , as well as the projects CPP2021/008643 and DTS24/00094 funded by the Spanish Ministry of Science and Innovation, projects PI22-00481 and PI25-00664 funded under the Accion Estrategica en Salud programme of the Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation) and the CIAICO/2023/168, CIAPOT/2024/19 and CIPROM/2022/43 PROMETEO project from Generalitat Valenciana. I.Canovas-Cervera thanks the Ministry of Science, Innovation, and Universities for FPU grant (FPU23/02919) J. Aparici-Collado would like to thank Agencia Espanola de Investigacion for a grant Torres Quevedo (PTQ2024-013788) .ElsevierDepartamento de Termodinámica AplicadaCentro de Biomateriales e Ingeniería TisularEscuela Técnica Superior de Ingeniería IndustrialGeneralitat ValencianaInstituto de Salud Carlos IIIAgencia Estatal de InvestigaciónMinisterio de Ciencia, Innovación y UniversidadesRepositorio Institucional de la Universitat Politècnica de València Riunet20262026-06-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://riunet.upv.es/handle/10251/235575reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valénciainstname:Universitat Politècnica de València (UPV)InglésengGeneralitat Valenciana https://doi.org/10.13039/501100003359 CIAICO%2F2023%2F168Generalitat Valenciana https://doi.org/10.13039/501100003359 CIAPOT%2F2024%2F19Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI22-00481Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI25-00664Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 CPP2021%2F008643Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 FPU23%2F02919Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 DTS24%2F00094Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 PTQ2024-013788open accesshttp://purl.org/coar/access_right/c_abf2Reconocimiento - No comercial (by-nc) http://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:dnet:riunet______::7849b6fb394375db0e9cc5746652b8482026-06-13T07:49:27Z |
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