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Establishment of Patient-Derived Organoids from Hepatocellular Carcinoma: Preliminary Data on Yield, Histopathological Concordance, and Methodological Challenges
by
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Oriana Lo Re
1
,
Christian Corti
2,
Lucia Cerrito
3,
Eleonora Cesari
2,
Elisabetta Creta
3,
Flavio De Maio
4,5,
Alessia Di Prima
1,
Vincenzo Facciuto
3,
Clelia Ferraro
1,
Eleonora Huqi
6,
Rosa Liotta
1,7,
Margot Lo Pinto
1,
Duilio Pagano
1,7
,
Riccardo Perriera
1,
Valentina Petito
6,
Giulia Santarelli
4,5,
Francesco Santopaolo
3,
Leonardo Stella
3,8,
Floriana Tortomasi
1,
Claudio Sette
2,9,
Salvatore Gruttadauria
1,10
,
Felice Giuliante
11,
Giovanni Zito
1
and
Francesca Romana Ponziani
3,6,12,*add
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1
Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione ISMETT IRCCS, 90127 Palermo, Italy
2
GSTep Organoids Research Core Facility, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
3
Liver Unit, CeMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
4
Department of Laboratory and Hematological Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
5
Microbiota Analysis & Microbial WGS Research Core Facility, GSTeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
6
CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
7
University of Pittsburgh Medical Center UPMC Italy, 90127 Palermo, Italy
8
Department of Life Science, Link Campus University, 00165 Rome, Italy
9
Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, 00168 Rome, Italy
10
Department of Surgery and Medical and Surgical Specialties, University of Catania, 95124 Catania, Italy
11
Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
12
Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
Cells 2026, 15(2), 125; https://doi.org/10.3390/cells15020125 (registering DOI)
Submission received: 4 November 2025
/
Revised: 15 December 2025
/
Accepted: 25 December 2025
/
Published: 10 January 2026
(This article belongs to the Section Tissues and Organs)
Simple Summary
Patient-derived organoids (PDOs) are emerging as powerful preclinical tools for modeling hepatocellular carcinoma (HCC). However, current data on their establishment efficiency, histopathological fidelity, and immunophenotypic correspondence remain limited and inconsistent. In this study, we present preliminary data from a PDO platform derived from HCC specimens, with an in-depth focus on methodological aspects, success rates, and comparison with the original tumor. Our findings aim to support reproducibility and offer a potential benchmark for future research in the field of organoid-based precision oncology.
Abstract
Patient-derived organoids (PDOs) have emerged as promising preclinical models for studying tumor biology and testing therapeutic strategies in oncology. These three-dimensional culture systems retain key histological, genetic, and functional characteristics of the original tumors, offering a unique opportunity to advance personalized medicine approaches in liver cancer. In this study, we present the methodological framework and preliminary findings of a prospective study aimed at generating and characterizing PDOs from patients with hepatocellular carcinoma (HCC) undergoing surgical resection. Tumor specimens were processed using an optimized protocol for organoid derivation, expansion, and cryopreservation. We evaluated the success rate of organoid establishment and the histo-molecular fidelity to the parental tumor. These early results demonstrate promising engraftment efficiency and maintenance of tumor-specific markers across passages. Our work highlights the potential of PDOs as a reliable and scalable platform for translational research in HCC, setting the stage for future applications in drug screening and biomarker discovery.
