Recent Advances in Liver Repair Strategies

A topical collection in Cells (ISSN 2073-4409). This collection belongs to the section "Cellular Pathology".

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Guest Editor
Laboratory of Pediatric Hepatology and Cell Therapy, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain, Louvain-la-Neuve, Belgium
Interests: liver cell therapy; mesenchymal stem cells; liver regeneration; hepatogenic differentiation; liver defects; cell therapy; liver cell types
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Topical Collection Information

Dear Colleagues,

The liver is a masterful organ that orchestrates the coordination of over 500 functions essential for life. Compared with other organs, the liver displays a high ability to regenerate itself—a well-conserved feature from fish to humans—which is crucial to preserve the coordination of those critical functions. Because such a complex and critical organ may experience several problems, keeping the liver healthy is a necessity to maintain its regeneration potential. Once this ability is altered, significant structural and functional changes occur that could alter other organs.

Liver diseases—either inherited or acquired—are continuously increasing, and represent a significant cause of mortality worldwide. Orthotopic liver transplantation (OLT) remains the gold standard therapeutic option. Unfortunately, it is not widely accessible to all patients for several reasons, among which is the significantly increased donor scarcity. Accordingly, investigations are continuously conducted to develop novel and innovative therapeutic strategies that could support and/or substitute OLT. This could be achieved via the improvement and strengthening of our knowledge on liver diseases, as well as on the underlined cellular and molecular mechanisms hampering the liver regeneration potential.

This Topical Collection will address all aspects related to liver biology, liver diseases, and early proof of concept investigations that are developing novel clinical solutions. It welcomes high-quality basic and clinical research papers as well as reviews that emphasize these issues.

Dr. Mustapha Najimi
Guest Editor

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Keywords

  • liver
  • liver diseases
  • signaling pathway
  • cell therapy
  • tissue engineering
  • gene therapy
  • transplantation
  • stem cells
  • tissue regeneration

Published Papers (2 papers)

2022

Jump to: 2021

19 pages, 4104 KiB  
Article
Human Allogeneic Liver-Derived Progenitor Cells Significantly Improve NAFLD Activity Score and Fibrosis in Late-Stage NASH Animal Model
by Mustapha Najimi, Sébastien Michel, Maria M. Binda, Kris Gellynck, Nathalie Belmonte, Giuseppe Mazza, Noelia Gordillo, Yelena Vainilovich and Etienne Sokal
Cells 2022, 11(18), 2854; https://doi.org/10.3390/cells11182854 - 13 Sep 2022
Cited by 1 | Viewed by 4127
Abstract
Accumulated experimental and clinical evidence supports the development of human allogeneic liver-derived progenitor cells (HALPCs) to treat fibro-inflammatory liver diseases. The aim of the present study was to evaluate their therapeutic effect in a non-alcoholic steatohepatitis (NASH)-STAM mouse model. The immune signaling characteristics [...] Read more.
Accumulated experimental and clinical evidence supports the development of human allogeneic liver-derived progenitor cells (HALPCs) to treat fibro-inflammatory liver diseases. The aim of the present study was to evaluate their therapeutic effect in a non-alcoholic steatohepatitis (NASH)-STAM mouse model. The immune signaling characteristics of HALPCs were first assessed in vitro. Upon inflammation treatment, HALPCs secreted large amounts of potent bioactive prostaglandin E2 and indoleamine 2,3-dioxygenase, which significantly reduced CD4+ T-lymphocyte proliferation and secretion of proinflammatory cytokines. In vivo, HALPCs were intravenously administered as single or triple shots (of a dose of 12.5 × 106 cells/kg BW) in STAM mice. Transplantation of HALPCs was associated with a significant decrease in the NAFLD activity score at an early stage and in both inflammation and hepatocyte ballooning scores in late-stage NASH. Sirius red staining analyses revealed decreased collagen deposition in the pericentral region at both stages of NASH. Altogether, these findings showed the anti-inflammatory and anti-fibrotic features of HALPCs in an in vivo NASH model, which suggests their potential to reverse the progression of this chronic fibro-inflammatory disease. Full article
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2021

Jump to: 2022

13 pages, 4928 KiB  
Article
Ultrastructural Profile Combined with Immunohistochemistry of a Hepatic Progenitor Cell Line in Pediatric Autoimmune Hepatitis: New Insights into the Morphological Pattern of the Disease
by Joanna Maria Lotowska, Maria Elzbieta Sobaniec-Lotowska and Piotr Sobaniec
Cells 2021, 10(8), 1899; https://doi.org/10.3390/cells10081899 - 27 Jul 2021
Cited by 4 | Viewed by 2324
Abstract
Considering that the heterogenic population of a hepatic progenitor cell line (HPCL) can play a vital role in autoimmune hepatitis (AIH), we decided to conduct pioneering retrospective evaluation of these cells in pediatric AIH by means of transmission electron microscopy (TEM). The aim [...] Read more.
Considering that the heterogenic population of a hepatic progenitor cell line (HPCL) can play a vital role in autoimmune hepatitis (AIH), we decided to conduct pioneering retrospective evaluation of these cells in pediatric AIH by means of transmission electron microscopy (TEM). The aim of the study was to assess the ultrastructure of the HPCL in children with untreated AIH. Ultrastructural analysis of the HPCL population, preceded by immunohistochemical staining for cytokeratin 7 (CK7), was performed using pretreatment liver biopsies from 23 children with clinicopathologically diagnosed AIH. Immunohistochemical assessment for CK7 allowed detection of proliferating immature epithelial cells differentiating towards periportal and intralobular intermediate hepatocytes without marked formation of ductular reactions in AIH children. Using TEM, we distinguished three morphological types of HPCs: I—the most undifferentiated progenitor cells; III—intermediate hepatocyte-like cells; II—intermediate bile duct cells. Most frequent were the cells differentiating towards hepatocytes, most rare—those differentiating towards cholangiocytes. The results indicate that an HPCL may be an important source of hepatocyte regeneration. Ultrastructural analyses of the HPCL population, combined with immunohistochemistry for CK7, might be a useful tool to evaluate liver cell regeneration, including fibrogenesis, and may help better understand the morphological pattern of the disease, in pediatric AIH. Frequent appearance of an HPCL in the vicinity of fibrotic foci, often accompanied by hyperactive Kupffer cells and transitional hepatic stellate cells, may indicate their significant involvement in liver fibrogenesis. Full article
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Figure 1

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