Improved in vivo efficacy of clinical-grade cryopreserved human hepatocytes in mice with acute liver failure

Donato, M. Teresa; Bolonio, Miguel; Cabezas, Estefanía; Pelechá, María; Pareja, Eugenia; Domènech, Anna; Castell, José V.; Gómez-Lechón, Marı́a José; Tolosa, Laia

doi:10.1016/j.jcyt.2019.12.005

Cited by 5 publications

(4 citation statements)

References 44 publications

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“…43 Improvements in parameters such as in vitro apoptosis, in vivo survival, and engraftment (by 4-fold) in APAP-injured mice, were achieved by optimising the cryopreservation medium. 44 Thawed hepatocytes display features consistent with early apoptosis. Caspase inhibitors mitigate stress response pathway activation, restoring cell attachment ability and metabolic function.…”

Section: Overcoming the Challenges Of Cell Therapy For Liver Diseasementioning

confidence: 98%

Cell therapy for advanced liver diseases: Repair or rebuild

Dwyer¹,

Macmillan²,

Brennan³

et al. 2021

Journal of Hepatology

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Advanced liver disease presents a significant worldwide health and economic burden and accounts for 3.5% of global mortality. When liver disease progresses to organ failure the only effective treatment is liver transplantation, which necessitates lifelong immunosuppression and carries associated risks. Furthermore, the shortage of suitable donor organs means patients may die waiting for a suitable transplant organ. Cell therapies have made their way from animal studies to a small number of early clinical trials. Herein, we review the current state of cell therapies for liver disease and the mechanisms underpinning their actions (to repair liver tissue or rebuild functional parenchyma). We also discuss cellular therapies that are on the clinical horizon and challenges that must be overcome before routine clinical use is a possibility.

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Section: Overcoming the Challenges Of Cell Therapy For Liver Diseasementioning

confidence: 98%

Cell therapy for advanced liver diseases: Repair or rebuild

Dwyer¹,

Macmillan²,

Brennan³

et al. 2021

Journal of Hepatology

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“…The number of people requiring transplantation of damaged livers is increasing, while the number of potential donors is still insufficient. The significance of research on new alternative therapies, including stem cell therapy, for the treatment of liver damaged by chemical agents or viruses results from the ineffectiveness of the currently used therapeutic methods based on liver or hepatocyte transplantation [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Efficacy of Two Routes of Administration of Human Amniotic Epithelial Cells in Cell Therapy of Acute Hepatic Insufficiency

Wieczorek,

Czekaj,

Król

et al. 2024

Pharmaceuticals

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The route of administration of implanted cells may affect the outcome of cell therapy by directing cell migration to the damaged site. However, the question of the relationship between the route of administration, the efficacy of colonisation of a given organ, and the efficacy of cell therapy has not been resolved. The aim of the study was to localise transplanted intravenously and intraperitoneally human amniotic epithelial cells (hAECs) in the tissues of mice, both healthy and injured, in an animal experimental model of acute liver failure (ALF). Mice intoxicated with D-Galactosamine (D-GalN) at a dose of 150 mg/100 g body weight received D-GalN alone or with a single dose of hAECs administered by different routes. Subsequently, at 6, 24, and 72 h after D-GaIN administration and at 3, 21, and 69 h after hAEC administration, lungs, spleen, liver, and blood were collected from recipient mice. The degree of liver damage and regeneration was assessed based on biochemical blood parameters, histopathological evaluation (H&E staining), and immunodetection of proliferating (Ki67+) and apoptotic (Casp+) cells. The biodistribution of the administered cells was based on immunohistochemistry and the identification of human DNA. It has been shown that after intravenous administration, in both healthy and intoxicated mice, most of the transplanted hAECs were found in the lungs, while after intraperitoneal administration, they were found in the liver. We concluded that a large number of hAECs implanted in the lungs following intravenous administration can exert a therapeutic effect on the damaged liver, while the regenerative effect of intraperitoneally injected hAECs on the liver was very limited due to the relatively lower efficiency of cell engraftment.

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“…The use of 3D cell formats has also been successful in processes of cryopreservation and post-thawing, improving in vivo efficacy [28]. Furthermore, applying good manufacturing practices (GMPs) improves hepatic functions and the ability to engraft in vivo, compared to the classic organ storage solution based on the University of Wisconsin medium [61].…”

Section: Isolation and Culture Of Hepatocytesmentioning

confidence: 99%

Recent Advances in Practical Methods for Liver Cell Biology: A Short Overview

Torres

Abdullah²,

Brol

et al. 2020

IJMS

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Molecular and cellular research modalities for the study of liver pathologies have been tremendously improved over the recent decades. Advanced technologies offer novel opportunities to establish cell isolation techniques with excellent purity, paving the path for 2D and 3D microscopy and high-throughput assays (e.g., bulk or single-cell RNA sequencing). The use of stem cell and organoid research will help to decipher the pathophysiology of liver diseases and the interaction between various parenchymal and non-parenchymal liver cells. Furthermore, sophisticated animal models of liver disease allow for the in vivo assessment of fibrogenesis, portal hypertension and hepatocellular carcinoma (HCC) and for the preclinical testing of therapeutic strategies. The purpose of this review is to portray in detail novel in vitro and in vivo methods for the study of liver cell biology that had been presented at the workshop of the 8th meeting of the European Club for Liver Cell Biology (ECLCB-8) in October of 2018 in Bonn, Germany.

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Improved in vivo efficacy of clinical-grade cryopreserved human hepatocytes in mice with acute liver failure

Cited by 5 publications

References 44 publications

Cell therapy for advanced liver diseases: Repair or rebuild

Cell therapy for advanced liver diseases: Repair or rebuild

Comparison of the Efficacy of Two Routes of Administration of Human Amniotic Epithelial Cells in Cell Therapy of Acute Hepatic Insufficiency

Recent Advances in Practical Methods for Liver Cell Biology: A Short Overview

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