Programa del congreso

El cáncer y las enfermedades cardiovasculares son las principales causas de mortalidad a nivel mundial, lo que pone en evidencia la necesidad de desarrollar nuevos tratamientos. Entre otras razones, dicho progreso farmacológico se ve limitado por la carencia de modelos predictivos de la patología cardíaca humana. Este estudio sienta las bases para su desarrollo en forma de corazón-en-chip endotelizado, al esperarse que en barrera endotelial se establezcan interacciones entre los tres principales tipos celulares cardíacos y mimetice el impedimento natural de la vasculatura sanguínea a la distribución de terapias, uno de los cuellos de botella más generalizados en los ensayos de nuevas terapias avanzadas.

CAR-T cell therapies have transformed the treatment of hematologic malignancies, yet their efficacy in solid tumors and myeloid leukemias remains limited. A major barrier is the tumor microenvironment (TME), which is enriched in immunosuppressive mediators, metabolic constraints, and dense extracellular matrices that restrict immune activity.

In this study, microfluidic devices combined with engineered three-dimensional (3D) matrices were employed to reproduce the bone marrow microenvironment of acute myeloid leukemia and to analyze how extracellular matrix (ECM) composition and effector–target localization influence CAR-T function. Jurkat triple reporter (TPR) cells, stably expressing fluorescent reporters for NF-κB (CFP), NFAT (eGFP), and AP-1 (mCherry), were transduced with a CD33-directed CAR to enable real-time monitoring of signaling events upon recognition of AML targets. HL60 cells, characterized by high CD33 expression, were used as target cells.

Specific activation of CAR-TPR effector cells was detected in collagen I matrices, with enhanced responses upon direct effector–target contact. Comparative analyses revealed that softer collagen matrices supported higher effector activation than denser or hydroxyapatite (HA)-supplemented conditions.

These findings indicate that matrix stiffness and mineralization critically regulate CAR-T activation within the leukemic niche and underscore the importance of incorporating biomechanical parameters into preclinical models for immunotherapy development in AML.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a rare, inherited arrhythmia linked to mutations in calcium-handling genes like RYR2. Children and adolescents are commonly affected, if untreated, carries a high risk of sudden cardiac death, with up to 31% of patients dying by the age of 30. The condition involves abnormal Ca²⁺ cycling, causing delayed afterdepolarizations (DADs) and triggered activity, which are difficult to reproduce in existing models. We present a heart-on-a-chip platform that integrates HL-1 cardiomyocytes, GCaMP6 Ca²⁺ sensors, and fabricated interdigitated electrodes to reproduce CPVT dynamics and evaluate anti-arrhythmic drugs in real time. Drug treatment with flecainide (50 μM) maintained Ca²⁺ amplitude of 0.35 ΔF/F, while reducing the beat rate to 31 beats/min under 1 Hz pacing, yielding a highly stable rhythm. At a higher dose (100 μM), flecainide further reduced the rate to 27 beats/min but also suppressed Ca²⁺ transient amplitude to 0.12 ΔF/F₀. These dose-dependent effects underscore the platform’s ability to capture both rhythm stabilization and drug-induced modulation of Ca²⁺ handling, providing a powerful tool for mechanistic studies and therapeutic screening in CPVT.

En este trabajo analizamos las fases iniciales de la formación de capilares (angiogénesis) desde la perspectiva de la monocapa celular y su interacción con los capilares. Para ello modelamos la monocapa celular como fluido activo con estructura nemática, de la cual emergen naturalmente dos longitudes características: la longitud de polaridad ℓp y la longitud visco–friccional λ. Esto nos permite analizar dos regímenes bien definidos que controlan la posibilidad de obtener condiciones para la migración colectiva de células desde la monocapa al capilar.

The study of cell behavior, including migration, proliferation, and differentiation in response to growth factors, is fundamental for understanding tissue regeneration and engineered microenvironments. Previous computational studies have often assumed a constant or pre-defined gradient of growth factors, which does not fully capture the dynamic and localized release patterns observed in reality. In this work, we present a computational model that incorporates the time-dependent release of growth factors from porous microcapsules embedded within the extracellular matrix (ECM). The release mechanism is governed by Fick’s law of diffusion with a spatially varying diffusion coefficient (capsule core, porous membrane, and ECM).

Cell migration is modeled through a stress-strain equilibrium framework, while the cell maturation index (MI) is introduced as a time-dependent parameter that regulates key biological processes, including proliferation, differentiation, maturation, and apoptosis. The finite element method is employed to solve the coupled system of equations describing diffusion, mechanics, and cellular dynamics. Model predictions are compared with previously reported experimental results to ensure biological relevance and consistency.

Simulation results demonstrate that cells initially migrate toward the central region of the ECM, where mechanical stiffness is highest, before progressing toward the microcapsules as growth factors diffuse outward. Furthermore, the spatial arrangement of microcapsules is shown to significantly influence the directionality and extent of cell migration, highlighting the importance of controlled release strategies in regulating cellular behavior. This framework provides a versatile computational tool for studying localized drug delivery systems and their impact on cell-microenvironment interactions.

The COVID-19 pandemic showed the need for novel preclinical models that accurately replicate human physiology and immune responses. Conventional in vitro systems lack tissue complexity and physiologically relevant microenvironments, while animal models differ from humans in respiratory anatomy, cellular composition, and immune function, severely limiting the translation of results. To address these limitations, we developed a hybrid human lung organoid model by integrating lung epithelial cells, stromal cells, macrophages, and NK cells. Progenitor cells were isolated from human lung resections, expanded as organoids, and combined with tissue-resident stromal cells and peripheral blood immune cells isolated via magnetic cell sorting, in a three-dimensional architecture via Matrigel domes. The co-culture system was able to sustain cell viability and promoted self-organization, enabling cell–cell communication within the three-dimensional architecture of the model. Upon infection with SARS-CoV-2, viral RNA and infectious titers peaked at 24 hours post-infection, followed by a gradual decline. Quantification of subgenomic viral RNA confirmed active viral replication. Infection induced expression of transcripts compatible with an innate immune response, with significant upregulation of IL-6, CXCL10, TNF-α, IFN-β, CCL5, and interferon-stimulated genes ISG15 and MX1. This hybrid organoid model overcomes critical limitations of classical systems by integrating multiple human lung cell types in a physiologically relevant environment. It supports productive SARS-CoV-2 infection and recapitulates early innate immune responses, providing a robust platform for investigating viral pathogenesis and evaluating therapeutic interventions for COVID-19 and other respiratory diseases.