2024/07/17

Researchers from CIC bioGUNE develop a 3D liver model with application in pharmaceutical industry for developing safer antitumoral drugs

Researchers from the Exosomes Laboratory at CIC bioGUNE led by Juan Manuel Falcón, Ikerbasque Research Professor, have developed an advanced three-dimensional model for the study of the interaction of primary healthy hepatocytes and tumor cells.
This new model, published in the journal Biomedicines, enables the extracellular vesicles secretion, as well as a more precise understanding of cellular interactions and drug responses in an environment that better simulates in vivo conditions.

The project led by Félix Royo, senior postdoc of the Exosomes Laboratory at CIC bioGUNE, member of BRTA, and CIBEREHD research network, have generated an advanced three-dimensional model with clear applications for pharmaceutical industry interested in finding drugs with selectivity for tumoral cells diminishing the occurrence of secondary effects.

The results of this study, detailed in a recent publication in the journal Biomedicines, represent a significant advance in understanding cellular interactions and drug responses in an environment that more faithfully simulates in vivo conditions.

This model uses primary hepatocytes cultured in ultra-low adhesion plates to form spheroids, both independently and in co-culture with tumor cells. These spheroids reproduce key physiological characteristics and allow the investigation of drug susceptibility and other related aspects.

The generated spheroids present a multicellular structure that includes an active outer layer and an internal mass of cellular debris, which was analyzed using histological staining techniques. Additionally, extracellular vesicles were isolated from the conditioned medium and their role in the dynamics of the spheroids and their response to cytotoxic treatments was studied. The research revealed distinct patterns of cellular distribution when co-cultivated with tumor cells, affecting the spheroids' conformation and response to antitumor drugs.

These findings position the model as a valuable tool for high-throughput studies and for investigating the specific effects of treatments on healthy and tumor cells in a more physiological environment than conventional two-dimensional models. Furthermore, it opens new possibilities for future research, including the detailed analysis of extracellular vesicles and the exploration of new therapies for hepatocellular carcinoma and other types of cancer.

This work has been funded by the Excellence Severo Ochoa grant Innovative Research Grant (SEV-2016-0644) and it also receives support from CIBER EHD-BBN COLLABORATION PROJECTS 2021. The project was funded by the European Union, EVCA Twining Project (Horizon GA n° 101079264) and nº 101095679 (HORIZON-HLTH-2022-STAYHLTH-02). The Spanish Ministry of Science and Innovation support this study with “Proyecto PID2021-125104OB-I00” financed by MCIN/ AEI /10.13039/501100011033/, and by FEDER “Una manera de hacer Europa”.

Reference: Félix Royo, Clara Garcia-Vallicrosa, Maria Azparren-Angulo, Guillermo Bordanaba-Florit, Silvia López-Sarrio and Juan Manuel Falcón-Pérez. Three-Dimensional Hepatocyte Spheroids: Model for Assessing Chemotherapy in Hepatocellular Carcinoma. Biomedicines. DOI: 10.3390/biomedicines12061200.

About CIC bioGUNE
The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organization conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.

About Ikerbasque
Ikerbasque - Basque Foundation for Science - is the result of an initiative of the Department of Education of the Basque Government that aims to reinforce the commitment to scientific research by attracting, recovering and consolidating excellent researchers from all over the world. Currently, it is a consolidated organization that has 290 researchers/s, who develop their work in all fields of knowledge.

About BRTA
BRTA is an alliance of 4 collaborative research centers (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 13 technology centers (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Leartiker, Lortek, Neiker, Tecnalia, Tekniker y Vicomtech) with the main objective of developing advanced technological solutions for the Basque corporate fabric.

With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three territories, the alliance seeks to promote collaboration between the research centrescenters, strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness and outspreading the Basque scientific-technological capacity abroad.

BRTA has a workforce of 3,500 professionals, executes 22% of the Basque Country's R&D investment, registers an annual turnover of more than 300 million euros and generates 100 European and international patents per year.

Spanish version