Cell transplantation-based regenerative medicine in liver diseases

Vincenzo Cardinale; Nicolas Lanthier; Pedro M Baptista; Guido Carpino; Gianluca Carnevale; Giuseppe Orlando; Roberta Angelico; Tommaso Maria Manzia; Detlef Schuppan; Massimo Pinzani; Domenico Alvaro; Rachele Ciccocioppo; Basak E Uygun

doi:10.1016/j.stemcr.2023.06.005

Cell transplantation-based regenerative medicine in liver diseases

Stem Cell Reports. 2023 Aug 8;18(8):1555-1572. doi: 10.1016/j.stemcr.2023.06.005.

Authors

Affiliations

¹ Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy. Electronic address: vincenzo.cardinale@uniroma1.it.
² Service d'Hépato-gastroentérologie, Cliniques Universitaires Saint-Luc, Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
³ Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas (CIBERehd), Madrid, Spain; Fundación ARAID, Zaragoza, Spain; Department of Biomedical and Aerospace Engineering, Universidad Carlos III de Madrid, Madrid, Spain.
⁴ Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Sapienza University of Rome, Italy.
⁵ Department of Surgery, Medicine, Dentistry, and Morphological Sciences with Interest in Transplant, Oncology, and Regenerative Medicine, University of Modena and Reggio Emilia, 41125 Modena, Italy.
⁶ Section of Transplantation, Department of Surgery, Wake Forest University School of Medicine, Winston Salem, NC, USA.
⁷ Hepatobiliary Surgery and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy.
⁸ Institute of Translational Immunology, Research Center for Immune Therapy, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁹ UCL Institute for Liver and Digestive Health, Division of Medicine, Royal Free Hospital, London, UK.
¹⁰ Department of Translation and Precision Medicine, "Sapienza" University of Rome, Rome, Italy.
¹¹ Gastroenterology Unit, Department of Medicine, A.O.U.I. Policlinico G.B. Rossi & University of Verona, Verona, Italy. Electronic address: rachele.ciccocioppo@univr.it.
¹² Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Shriners Hospitals for Children, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: buygun@mgh.harvard.edu.

Abstract

This review aims to evaluate the current preclinical state of liver bioengineering, the clinical context for liver cell therapies, the cell sources, the delivery routes, and the results of clinical trials for end-stage liver disease. Different clinical settings, such as inborn errors of metabolism, acute liver failure, chronic liver disease, liver cirrhosis, and acute-on-chronic liver failure, as well as multiple cellular sources were analyzed; namely, hepatocytes, hepatic progenitor cells, biliary tree stem/progenitor cells, mesenchymal stromal cells, and macrophages. The highly heterogeneous clinical scenario of liver disease and the availability of multiple cellular sources endowed with different biological properties make this a multidisciplinary translational research challenge. Data on each individual liver disease and more accurate endpoints are urgently needed, together with a characterization of the regenerative pathways leading to potential therapeutic benefit. Here, we critically review these topics and identify related research needs and perspectives in preclinical and clinical settings.

Keywords: acute liver failure; cell therapy; cirrhosis; hepatocytes; macrophages; progenitors; scaffolds; stem cells.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Hepatocytes
Humans
Liver / metabolism
Liver Diseases* / metabolism
Liver Diseases* / therapy
Regenerative Medicine* / methods
Stem Cell Transplantation

Grants and funding

R01 DK084053/DK/NIDDK NIH HHS/United States