Macrophage therapy for liver fibrosis and regeneration

Abstract

The liver has a population of resident macrophages termed Kupffer cells that are phagocytic and aid fi ltration of the portal blood. Following liver injury both the resident macrophages and circulating monocytes infl uence both liver regeneration and liver fi brosis. Kupffer cells can stimulate hepatocyte proliferation via the secretion of IL-6; macrophages stimulate a ductular proliferation via TWEAK secretion and also secrete Wnts which stimulate liver regeneration. Macrophages can both promote fi brosis and help resolve fi brosis depending upon the phase of liver injury. We have been developing macrophage therapy for liver fi brosis and found that injected mature macrophages promote scar resolution in mouse models of liver fi brosis via a number of direct mechanism such as MMP expression but also in indirectly via the expression of chemokines which aid the recruitment of infl ammatory cells to the scar area and promote scar resolution. Based on these basic research results, we are planning human studies of autologous macrophage therapy for liver cirrhosis in the near future.