title: Control of IBMIR Induced by Fresh and Cryopreserved Hepatocytes by Low Molecular Weight Dextran Sulfate Versus Heparin.
abstract: Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 μg/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze-thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze-thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 μg/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Gustafson
authors.forename: Sana
authors.initials: S
authors.lastname: Asif
authors.forename: Huda
authors.initials: H
authors.lastname: Kozarcanin
authors.forename: Graciela
authors.initials: G
authors.lastname: Elgue
authors.forename: Staffan
authors.initials: S
authors.lastname: Meurling
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Ekdahl
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
mesh_terms: D015925:Cryopreservation / Q000379:methods*; D016264:Dextran Sulfate / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D006493:Heparin / Q000627:therapeutic use*; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007118:Immunoassay; D007249:Inflammation / Q000517:prevention & control; D008099:Liver / Q000166:cytology; D008970:Molecular Weight; D014183:Transplantation, Heterologous / Q000379:methods
chemical_list: D006493:Heparin; D016264:Dextran Sulfate