人iPSC来源肝类器官模型再现Wolman病多细胞组织反应并实现治疗性挽救

Acknowledgments

The authors thank all the members of ADM lab at ICGEB for insightful discussions and Marco Bestagno from ICGEB for the technical support for the FACS analysis. Furthermore, we would like to thank Brassier Anaïs for helping in procuring patient samples. The figures in this work were created with BioRender (https://BioRender.com).

Funding

G.S. is funded by grants from: Telethon (GGP20031) and Italian Ministry of University and Research and European Union under NextGenerationEU “Progetti di rilevante interesse nazionale” (PRIN): PRIN prot. no.2022PWKZXE; PNRR M4C2 INV 1.1, PRIN 2022 prot. no. P2022A9J9L; NRRP NextGenerationEU Project CN00000041-National Center for Gene Therapy and Drugs based on RNA Technology; AIRC (Start-Up 2020 – ID. 24322 project – PI G.S.). M.A. is funded by the French National Research Agency (grants: NEEDED ANR -24-CE18-3712-01). This study was partially funded by the Italian Ministry of University and Research (MUR) program, “Departments of Excellence 2023–2027”, the AGING Project—Department of Translational Medicine, University of Piemonte Orientale, and is part of the project, P2022E3BTH-CUP C53D23007600001, which received funding from NextGeneration EU-MUR M4C2–PRIN 2022 PNRR. G.D.S. is funded by the Fondazione AIRC IG grant 30570, the Fondazione AIRC Special Program Molecular Clinical Oncology “5 per mille” 22759, Worldwide Cancer Research (grant 24-0361), the NRRP NextGenerationEU Project CN00000041-National Center for Gene Therapy and Drugs based on RNA Technology, the Italian University and Research Ministry PRIN P2022ZWY8H and the PRIN 2022XBYNJP. R.B. was supported by an AIRC post-doc fellowship for Italy (ID: 29960).

Author information

Authors and Affiliations

International Centre for Genetic Engineering and Biotechnology (ICGEB), Laboratory of Advanced Disease Models, Area Science Park- Padriciano, Trieste, Italy
Davide Selvestrel, Caterina Da Rodda, Beatrice Anfuso, Suresh Velnati, Karin Hofmann & Giovanni Sorrentino
Genethon, 91000, Evry, France
Marine Laurent & Mario Amendola
Paris-Saclay University, Univ Evry, Inserm, Genethon, Integrate research unit UMR_S951, 91000, Evry, France
Marine Laurent & Mario Amendola
Department of Translational Medicine (DIMET), Center of Excellence in Aging Sciences, University of Piemonte Orientale, Novara, Italy
Annamaria Antona, Marcello Manfredi & Daniela Capello
Armenise-Harvard Laboratory of Cell Division, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy
Alessia Mattivi & Luca Fava
Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
Andrea Marfoglia, Deborah Bonazza, Fabrizio Zanconati, Manuela Mastronardi, Nicolò de Manzini, Silvia Palmisano & Giovanni Sorrentino
International Centre for Genetic Engineering and Biotechnology (ICGEB), Laboratory of Cancer Cell Signaling, Area Science Park- Padriciano, Trieste, Italy
Rebecca Bertolio & Giannino Del Sal
Laboratory of stem cell biology, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy
Luciano Conti
Department of Pathology, University Hospital Cattinara, Trieste, Italy
Deborah Bonazza & Fabrizio Zanconati
Surgical Clinic Unit, Cattinara Hospital, ASUGI, Strada di Fiume, 447, Trieste, Italy
Manuela Mastronardi, Nicolò de Manzini & Silvia Palmisano
Fondazione Italiana Fegato, Trieste, Italy
Natalia Rosso & Claudio Tiribelli
Center for Translational Research on Autoimmune and Allergic Diseases, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
Marcello Manfredi
UPO Biobank, University of Piemonte Orientale, Novara, Italy
Daniela Capello
Department of Medical Pathology and Biology, Paris Hospitals Public Assistance, Hôpital Necker, University Paris Cité, Paris, France
Philippe Drabent
Department of Life Sciences, University of Trieste, Trieste, Italy
Giannino Del Sal
IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy
Giannino Del Sal
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
Mario Amendola

Authors

Davide Selvestrel
Caterina Da Rodda
Beatrice Anfuso
Marine Laurent
Annamaria Antona
Alessia Mattivi
Suresh Velnati
Karin Hofmann
Andrea Marfoglia
Rebecca Bertolio
Luciano Conti
Deborah Bonazza
Fabrizio Zanconati
Manuela Mastronardi
Nicolò de Manzini
Natalia Rosso
Claudio Tiribelli
Marcello Manfredi
Daniela Capello
Philippe Drabent
Luca Fava
Silvia Palmisano
Giannino Del Sal
Mario Amendola
Giovanni Sorrentino

Corresponding author

Correspondence to Giovanni Sorrentino.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

All methods were performed in accordance with the relevant guidelines and regulations. The collection and use of human liver tissue for the generation of organotypic cultures were approved by the Comitato Etico Unico Regionale of Friuli Venezia Giulia, Italy (protocol no. 0033969, 26 August 2024). Written informed consent was obtained from all participants. All animal procedures from which the mouse samples used in this study were derived were approved by the ethical committee CEEA-51 (APAFIS no. 33620-2021101416506495) and were performed in accordance with French and European legislation governing animal experimentation. No identifiable images of human research participants are included in this article; therefore, separate consent for publication of identifiable images was not required.

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Selvestrel, D., Da Rodda, C., Anfuso, B. et al. Human iPSC-derived liver organoid model multicellular tissue responses and therapeutic rescue in Wolman disease. Cell Death Dis (2026). https://doi.org/10.1038/s41419-026-09345-1

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Received: 06 July 2026
Revised: 08 September 2026
Accepted: 27 September 2026
Published: 16 October 2026
DOI: https://doi.org/10.1038/s41419-026-09345-1