Hamostaseologie 2020; 40(S 01): S26-S31
DOI: 10.1055/a-1282-2286
Review Article

Molecular Profiling of Liver Sinusoidal Endothelial Cells in Comparison to Hepatocytes: Reflection on Which Cell Type Should Be the Target for Gene Therapy

Osman El-Maarri
1   Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany
,
Muhammad Ahmer Jamil
1   Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany
,
Johannes Oldenburg
1   Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany
› Author Affiliations
Funding This study was funded by Takeda Pharmaceuticals North America (H16-34964).

Abstract

Human factor VIII (FVIII), which deficiency leads to hemophilia A, is largely synthesized and secreted by the liver sinusoidal endothelial cells (LSECs). However, the characteristics of these cells that secrete FVIII are not well known. We have previously reported that based on genome-wide expression and CpG methylation profiling, LSECs have a distinct molecular profile that distinguishes them from other endothelial cells. Hepatocytes are targeted by gene therapy protocols to treat hemophilia A. However, the hepatocyte is not the natural site for FVIII synthesis and current gene therapy protocols are eliciting immune responses that require immune suppression with corticosteroid therapy in a fairly high proportion of patients over a significant period of time. Cellular stress because of ectopic FVIII expression and codon optimization are discussed as potential underlying mechanisms. Here, we highlight the molecular differences between LSECs and hepatocytes.



Publication History

Received: 29 September 2020

Accepted: 05 October 2020

Article published online:
13 November 2020

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