Significantly enhanced recovery of acute liver failure by liver targeted delivery of stem cells via heparin functionalization.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Acute liver failure (ALF) occurs by insufficient detoxification of toxic materials in the liver, generating excess reactive oxygen species (ROS). Mesenchymal stem cell (MSC) therapy can be a promising approach for the treatment of liver diseases including ALF by anti-inflammatory activity and secretion of cytokines associated with tissue regeneration. However, the efficacy of MSC therapy is generally poor, mainly due to a low survival and engraftment of administered cells. In this study, we demonstrated that the enhanced delivery of human adipose-derived stem cells (hADSCs) to the damaged liver by the coating of lipid-conjugated heparin could result in significantly improved recovery from ALF in a mouse model. First, the therapeutic effect of secretomes of hADSCs on acetaminophen (APAP)-induced hepatic cell damage was confirmed regardless of the coating of lipid-conjugated heparin on hADSCs in vitro. Then, the therapeutic effects of lipid-conjugated heparin coated hADSCs (Lip-Hep/hADSC group) were analyzed compared to hADSCs themselves (hADSC group) using an APAP-induced ALF model in vivo. Intravenous administration of hADSCs could lower the elevated serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), but Lip-Hep/hADSC group showed faster decrease in serum levels of AST and ALT to the normal values compared to hADSC group. Enhanced delivery and longer r

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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