Biology subjects

Lanz, H.

Publications and source records attributed to Lanz, H..

3 recordsLinked to original sources

bioRxiv2025

Modeling Hepatocellular Carcinoma and its microenvironment on a chip

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Its incidence is increasing and is closely related to advanced liver disease. Interactions in the HCC microenvironment between tumor cells and the associated stroma actively regulate tumor initiation, progression, metastasis, and therapy response. Effective drug development increasingly requires advanced models that can be utilized in the earliest stages of compound and target discovery. Here we report a phenotypic screen on an advanced HCC patient-derived chip (PDChip) model. The vascularized HCC PDChip models include relevant cellular players of the HCC microenvironment. We assessed the effect of 28 treatment conditions on a panel of 8 primary HCC tumors and 2 cell lines. Approximately 1200 HCC PDchips were grown under perfusion flow, exposed to treatments, and subsequently assessed for viability, tumor-associated vasculature responses and chemokine and cytokine changes. Although the SoC therapeutics sorafenib and lenvatinib reduced culture viability and produced profound changes in the organization of the vascular beds, they did not affect the tumor cell population in these cultures. Atorvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, reduced tumor viability but did not affect vascular bed organization. Sorafenib, lenvatinib and atorvastatin also affected chemokine and cytokine release. Tocilizumab, galunisertib, and vactosertib decreased the level of IL6, a relevant prognostic marker for HCC, while IL6 was increased by halofuginone. In conclusion, HCC PDChip models enabled a detailed evaluation of drug-induced responses in the tumor and associated microenvironment, highlighting their importance in preclinical research for understanding diseases and developing new drugs.

bioengineering↗

bioRxiv2025

A Novel Human Distal Tubuloid-On-A-Chip Model For Investigating Sodium And Water Transport Mechanisms

The distal segments of the nephron play a central role in regulating water and electrolyte balance, making them critical targets for therapeutic interventions. Damage to these segments is associated with significant health consequences. Studying their (patho)physiology in vivo remains challenging due to the kidneys complex architecture. Recent advances led to the development of more representative in vitro models, including human tubuloids that replicate the phenotype of distal tubule segments. Additionally, novel high throughput microfluidic systems, which support 3D cell culture under flow conditions, provide a platform for closely mimicking in vivo environments. This study presents an enhanced in vitro model of human distal tubule segments by integrating tubuloid culture with the OrganoPlate(R) platform. Tubuloid cells were grown as three-dimensional tubules against a collagen-1 matrix and under alternating flow condition, then differentiated into a distal phenotype. qPCR analysis demonstrated enhanced expression of distal segment markers in 3D flow cultures compared to traditional 2D models. Immunohistochemistry confirmed the formation of a leak-tight, highly polarized epithelium with apical and basolateral localization of key electrolyte transporters. Functional integrity was verified by restricted dextran diffusion and increased transepithelial resistance. Radiolabeled sodium assays revealed active and selective sodium transport mediated by apical epithelial sodium channels (ENaC) and basolateral Na/K ATPase. Sodium transport was followed by water movement, evidenced by dome formation beneath the epithelial monolayer. The models utility was further demonstrated in toxicity studies using trimethoprim, an antibiotic that inhibits ENaC function, resulting in reduced sodium transport and dome formation. This system enables the study of primary human tubule cells with a distal phenotype under controlled flow conditions, allowing direct assessment of water and salt transport. The model provides a valuable tool for investigating distal nephron (patho)physiology and facilitates high-throughput drug development and toxicity testing.

bioengineering↗

bioRxiv2024

Global 5-methylcytosine-RNA disruption reduces the vectorial competence to DENV2 of heatwave-exposed Aedes aegypti mosquitoes

Heatwaves are an increasingly common environmental event linked with climate change. Abnormally high heatwave temperatures can affect several mosquito vector traits that are determinants of pathogen transmission. Understanding how these mosquitoes adapt to high heat is vital for global public health. RNA methylation, a key cellular mechanism in stress response and adaptation, remains understudied in mosquito vector competence and heat stress responses. This study investigates the role of RNA methylation in mosquito responses to heatwaves and its influence on DENV2 vector competence. Heatwave-exposed and DENV-infected mosquitoes presented lower survivorship and lower antiviral transcriptional response, developed high infection rates, and increased the life expectancy of infected mosquitoes during the period of highest virus transmissibility. In contrast, inhibition of RNA methylation in heatwave-treated mosquitoes increased survivorship and the antiviral transcriptional response, reducing infection prevalence from 78% to 37%. These results indicate that the RNA methylation background in mosquitoes favors vector competence for DENV2 during a heatwave exposure, and points towards possible interventions to countermeasure the effect of climate change on DENV transmission.

molecular biology↗