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Tokodai K, Kumagai-Braesch M, Karadagi A, et al. Blood Group Antigen Expression in Isolated Human Liver Cells in Preparation for Implementing Clinical ABO-Incompatible Hepatocyte Transplantation. J Clin Exp Hepatol. 2019;10(2):106-113doi: 10.1016/j.jceh.2019.07.001.
Tokodai, K., Kumagai-Braesch, M., Karadagi, A., Johansson, H., Ågren, N., Jorns, C., Ericzon, B. G., & Ellis, E. (2020). Blood Group Antigen Expression in Isolated Human Liver Cells in Preparation for Implementing Clinical ABO-Incompatible Hepatocyte Transplantation. Journal of clinical and experimental hepatology, 10(2), 106-113. https://doi.org/10.1016/j.jceh.2019.07.001
Tokodai, Kazuaki, et al. "Blood Group Antigen Expression in Isolated Human Liver Cells in Preparation for Implementing Clinical ABO-Incompatible Hepatocyte Transplantation." Journal of clinical and experimental hepatology vol. 10,2 (2020): 106-113. doi: https://doi.org/10.1016/j.jceh.2019.07.001
Tokodai K, Kumagai-Braesch M, Karadagi A, Johansson H, Ågren N, Jorns C, Ericzon BG, Ellis E. Blood Group Antigen Expression in Isolated Human Liver Cells in Preparation for Implementing Clinical ABO-Incompatible Hepatocyte Transplantation. J Clin Exp Hepatol. 2020 Mar-Apr;10(2):106-113. doi: 10.1016/j.jceh.2019.07.001. Epub 2019 Jul 11. PMID: 32189925; PMCID: PMC7068001.
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J Clin Exp Hepatol. 2020 Mar-Apr;10(2):106-113. doi: 10.1016/j.jceh.2019.07.001. Epub 2019 Jul 11.

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

Journal of clinical and experimental hepatology

Kazuaki Tokodai, Makiko Kumagai-Braesch, Ahmad Karadagi, Helene Johansson, Nils Ågren, Carl Jorns, Bo-Göran Ericzon, Ewa Ellis

Affiliations

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

PMID: 32189925 PMCID: PMC7068001 DOI: 10.1016/j.jceh.2019.07.001

Abstract

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: 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: 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: 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.

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

Keywords: 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

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