Control of IBMIR induced by fresh and cryopreserved hepatocytes by low molecular weight dextran sulfate

• Published in: Cell transplantation 2017, Vol.26 (1), p.71
• Main Authors: Gustafson, Elisabet, Asif, Sana, Kozarcanin, Huda, Meurling, Staffan, Ekdahl, Kristina Nilsson, Nilsson, Bo
• Format: Article
• Language: English
• Subjects: Hepatocyte transplantation; IBMIR; Innate immunity; Low molecular weight dextran sulfate (LMW-DS); Thromboinflammation
• ISSN: 1555-3892; 0963-6897
• DOI: 10.3727/096368916X692609

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 mu g/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 mu g/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.