3D co-cultures of primary human hepatocytes and Kupffer-like cells to address innate immune responses to rAAV.

ABSTRACT: Recombinant adeno-associated viruses (rAAVs) are a platform of choice for gene therapy. However, liver-directed transduction has been hindered by immune responses unpredicted in the pre-clinical models, resulting in therapy failure. Liver immune responses are strictly regulated by the interactions between hepatocytes and non-parenchymal liver cells, such as Kupffer cells (the liver-resident macrophages) but how rAAVs induce such responses remains largely unknown. Therefore, human models recapitulating such interactions are required to address innate immune responses. Here, we developed a human 3D model to characterize the contribution of hepatocytes and Kupffer cells to the innate immune response. We developed a strategy for the differentiation of Kupffer-like cells from circulating monocy

SUBMITTER: Ramella Gal I 

PROVIDER: S-EPMC12795831 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature