# CCL2 supports human hepatocytes long-term expansion for bioartificial liver therapy to relieve acute liver failure and extrahepatic complications

## TL;DR

Scientists found that CCL2 helps human liver cells grow long-term in the lab, which could lead to better treatments for severe liver failure.

## Contribution

CCL2 is identified as a key factor enabling long-term expansion of human hepatocytes for bioartificial liver therapy.

## Key findings

- CCL2 promotes long-term expansion of human primary hepatocytes over 30 passages.
- CCL2-mediated hepatocyte proliferation supports bioartificial liver therapy in a porcine model.
- BAL therapy using CCL2 improves survival rates in acute liver failure by protecting extrahepatic organs.

## Abstract

The lack of expandable human hepatocytes in vitro hampers the clinical application of the bioartificial liver. Previous studies have shown that chemical cocktails containing growth factors can support long-term expansion of hepatocytes through dedifferentiation. Here, it is revealed that chemokine (C-C motif) ligand 2 (CCL2) is a key factor in liver regeneration. CCL2 could promote the long-term expansion (over 30 passages) of human primary hepatocytes and enhancing their proliferative efficiency. Subsequently, CCL2-mediated proliferation of hepatocytes can effectively expand in vitro, and repopulate the liver of Fah-/- mice following 2-(2-nitro-4-trifluoromethylbenzyol)-1,3- cyclohexanedione (NTBC) withdrawal. Further studies revealed that CCL2-mediated hepatocyte proliferation could yield a sufficient number of highly active and well-functioning hepatocytes, crucial for supporting Bioartificial liver (BAL) therapy in treating acute liver failure (ALF) in a porcine model. Mechanically, BAL therapy effectively suppresses inflammatory responses, promotes liver regeneration, and subsequently protects extrahepatic organs, leading to improved survival rates in ALF porcine models.