Elucidating the role of macrophages in liver regeneration and tissue unit formation

01 October 2019 → 31 August 2020
Research Foundation - Flanders (FWO)
Research disciplines
No data available
Macrophage Liver regeneration Cell-cell interactions
Project description

The liver has the unique ability to rapidly regenerate and restore function following tissue damage. This has been recognized as far back as the ancient Greeks, who described it in the myth of Prometheus. However, the precise mechanisms controlling regeneration have not yet been fully identified. Macrophages (Macs) have been proposed to play a role in regeneration, however, it has not been clear if these are Kupffer cells (KCs), tissue resident macs of the liver, or macs recruited during regeneration (rMacs). Previously available tools have not allowed a distinction to be drawn between these cells. Within the liver KCs and/or rMacs are in close proximity to hepatocytes, hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs), these cells together with liver macs can be thought of as a tissue unit, which needs to be rebuilt as the liver regenerates. Adopting this tissue unit view of the liver, we hypothesize that these cells interact with one another forming a stable circuit, the maintenance of which is required for normal liver regeneration. Here we propose the use of novel and innovative tools to study cell-cell cross-talk and conclusively determine the cell circuit signals driving the formation of new functional units. These findings will be of clinical relevance, as understanding the molecular and cellular circuits that underpin liver regeneration may yield therapies to boost liver regeneration and prevent the need for transplantation.