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

Project description

Cellular interplay during liver regeneration

The liver has a fundamental role in body homeostasis. Unlike any other organ, it exhibits an astounding capacity to regenerate upon injury and return to its prior size and weight. The EU-funded LiverMacRegenCircuit project is interested to delineate the role of resident and recruited macrophages in the process of liver regeneration. Researchers are working under the hypothesis that various cell types including macrophages and hepatocytes need to be replenished after injury. Investigation of the crosstalk between cell types and the signals required for maintaining the cell circuit will lead to a better understanding of the regeneration process and pave the way for regenerative interventions.

Objective

The liver, unlike many other tissues, has the ability to rapidly regenerate and restore function following tissue damage or surgical resection. This regenerative capacity has been recognized as far back as the ancient Greeks, who described it in the myth of Prometheus. Despite this, the precise molecular and cellular mechanisms underpinning the regeneration process are yet to be fully elucidated. Macrophages (Macs) have been proposed to play a role in regeneration but it has not been clear if these are Kupffer cells (KCs), the tissue resident macs of the liver, or macs recruited during the regeneration process (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 (HSC) and particularly liver sinusoidal endothelial cells (LSECs), these cells together with liver macrophages 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 including KC and tissue unit cell-specific knock in mice to study cell-cell cross-talk and conclusively determine the cell-circuit signals driving the formation of new functional units within the liver. With donor organs in short supply this project has the potential to uncover pro-regenerative therapies that are so desperately needed.

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2018

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Coordinator

VIB VZW
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 166 320,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 166 320,00
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