Improving engraftment of hepatocyte transplantation using alpha-1 antitrypsin as an immune modulater

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Authors

Lee, Charlotte
Dhawan, Anil
Iansante, Valeria
Filippi, Celine
Mitry, Ragai
Tang, Joanne
Walker, Simon
Fernandez DaCosta, Raquel
Sinha, Siddharth
Hughes, Robin D.

Issue Date

2019

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Article

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Abstract

For patients with non-cirrhotic liver-based metabolic disorders, hepatocyte transplantation can be an effective treatment. However, long-term function of transplanted hepatocytes following infusion has not been achieved due to insufficient numbers of hepatocytes reaching the liver cell plates caused by activation of the instant blood-mediated inflammatory reaction (IBMIR). Our aim was to determine if the natural immune modulator, alpha-1 antitrypsin (AAT), could improve engraftment of transplanted hepatocytes and investigate its mechanism of action. A tubing loop model was used to analyse activation of the IBMIR when human hepatocytes were in contact with ABO-matched blood and 4 mg/ml AAT. Platelet and white cell counts, complement and cytokine expression were analysed. To determine if AAT could improve short-term engraftment, female rats underwent tail vein injection of AAT (120 mg/kg) or water (control) prior to the intrasplenic transplantation of 2 × 10

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Journal of Molecular Medicine

Volume

97

Issue

4

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