Blood Group Antigen Expression in Isolated Human Liver Cells in Preparation for Implementing Clinical ABO-Incompatible Hepatocyte Transplantation.

ABO-incompatible transplantation ABOi, ABO-incompatible ABOi-HTx, ABO-incompatible hepatocyte transplantation C3a, Complement 3a CCA, Cholangiocarcinoma CRC, Colorectal cancer metastasis DCD, Donation after death DSA, Donor-specific anti-HLA antibody HCC, Hepatocellular carcinoma HTx, Hepatocyte transplantation IBMIR, Instant blood-mediated inflammatory reaction ICH, Intracranial hemorrhage IQR, Interquartile range MSCs, Mesenchymal stem cells blood group antigens hepatocytes

Journal

Journal of clinical and experimental hepatology
ISSN: 0973-6883
Titre abrégé: J Clin Exp Hepatol
Pays: India
ID NLM: 101574137

Informations de publication

Date de publication:
Historique:
received: 18 02 2019
accepted: 05 07 2019
entrez: 20 3 2020
pubmed: 20 3 2020
medline: 20 3 2020
Statut: ppublish

Résumé

ABO blood group antigens in the liver are expressed mainly on endothelial cells or biliary epithelial cells but not on hepatocytes. This suggests that ABO-incompatible hepatocyte transplantation (ABOi-HTx) is theoretically feasible. However, the effects of stress on ABO blood group antigen expression caused by isolation and intraportal infusion require thorough investigation before ABOi-HTx can be implemented in clinical settings. Human hepatocytes were isolated from liver tissue obtained from liver resection or deceased donor livers. The expression of blood group antigens on cryopreserved human liver tissues and isolated hepatocyte smear specimens were examined by immunofluorescent staining. The effect of proinflammatory cytokines on blood group antigen expression of hepatocytes was evaluated by flow cytometry. Instant blood-mediated inflammatory reaction after hepatocyte incubation with ABO-incompatible whole blood was examined using the tubing loop model. Blood group antigens were mainly expressed on vessels in the portal area. In hepatocyte smear specimens, isolated hepatocytes did not express blood group antigens. In contrast, a subset of cells in the smear specimens of nonparenchymal liver cells stained positive. In the flow cytometry analysis, isolated hepatocytes were negative for blood group antigens, even after 4-h incubation with cytokines. Platelet counts and complement activation were not significantly different in ABO-identical versus ABO-incompatible settings in the tubing loop model. Our study showed that blood group antigens were not expressed on hepatocytes, even after isolation procedures or subsequent incubation with cytokines. This finding is an important step toward removing the restriction of ABO matching in hepatocyte transplantation. Our results suggest that ABOi-HTx is a feasible therapeutic option, especially in patients who require urgent treatment with freshly isolated hepatocytes, such as those with acute liver failure.

Sections du résumé

BACKGROUND BACKGROUND
ABO blood group antigens in the liver are expressed mainly on endothelial cells or biliary epithelial cells but not on hepatocytes. This suggests that ABO-incompatible hepatocyte transplantation (ABOi-HTx) is theoretically feasible. However, the effects of stress on ABO blood group antigen expression caused by isolation and intraportal infusion require thorough investigation before ABOi-HTx can be implemented in clinical settings.
METHODS METHODS
Human hepatocytes were isolated from liver tissue obtained from liver resection or deceased donor livers. The expression of blood group antigens on cryopreserved human liver tissues and isolated hepatocyte smear specimens were examined by immunofluorescent staining. The effect of proinflammatory cytokines on blood group antigen expression of hepatocytes was evaluated by flow cytometry. Instant blood-mediated inflammatory reaction after hepatocyte incubation with ABO-incompatible whole blood was examined using the tubing loop model.
RESULTS RESULTS
Blood group antigens were mainly expressed on vessels in the portal area. In hepatocyte smear specimens, isolated hepatocytes did not express blood group antigens. In contrast, a subset of cells in the smear specimens of nonparenchymal liver cells stained positive. In the flow cytometry analysis, isolated hepatocytes were negative for blood group antigens, even after 4-h incubation with cytokines. Platelet counts and complement activation were not significantly different in ABO-identical versus ABO-incompatible settings in the tubing loop model.
CONCLUSION CONCLUSIONS
Our study showed that blood group antigens were not expressed on hepatocytes, even after isolation procedures or subsequent incubation with cytokines. This finding is an important step toward removing the restriction of ABO matching in hepatocyte transplantation. Our results suggest that ABOi-HTx is a feasible therapeutic option, especially in patients who require urgent treatment with freshly isolated hepatocytes, such as those with acute liver failure.

Identifiants

DOI: 10.1016/j.jceh.2019.07.001 PMID: 32189925 PMC: PMC7068001
pubmed: 32189925
doi: 10.1016/j.jceh.2019.07.001
pii: S0973-6883(19)30177-X
pmc: PMC7068001
doi:

Types de publication

Journal Article

Langues

eng

Pagination

106-113

Informations de copyright

© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.

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Auteurs

Kazuaki Tokodai (K)

Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute and Karolinska University Hospital Huddinge, Stockholm, SE-141 86, Sweden.

Makiko Kumagai-Braesch (M)

Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute and Karolinska University Hospital Huddinge, Stockholm, SE-141 86, Sweden.

Ahmad Karadagi (A)

Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute and Karolinska University Hospital Huddinge, Stockholm, SE-141 86, Sweden.

Helene Johansson (H)

Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute and Karolinska University Hospital Huddinge, Stockholm, SE-141 86, Sweden.

Nils Ågren (N)

Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute and Karolinska University Hospital Huddinge, Stockholm, SE-141 86, Sweden.

Carl Jorns (C)

Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute and Karolinska University Hospital Huddinge, Stockholm, SE-141 86, Sweden.

Bo-Göran Ericzon (BG)

Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute and Karolinska University Hospital Huddinge, Stockholm, SE-141 86, Sweden.

Ewa Ellis (E)

Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute and Karolinska University Hospital Huddinge, Stockholm, SE-141 86, Sweden.

Classifications MeSH