Journal of Clinical Hepatology
Macrophages can either promote inflammation or help repair damaged tissue, making them potential tools for treating liver cirrhosis. However, inflammatory M1 macrophages also produce Wnt5a, a signaling protein that may contribute to fibrosis.
Researchers investigated whether reducing Wnt5a expression could improve the therapeutic activity of M1 bone marrow-derived macrophages. They created a rat model of liver cirrhosis and compared untreated animals with rats receiving unmodified macrophages, macrophages carrying an empty genetic vector, or macrophages in which Wnt5a had been knocked down.
All macrophage-treated groups showed less liver inflammation, lower liver-enzyme levels and reduced collagen deposition compared with untreated cirrhotic rats. The Wnt5a-silenced macrophages produced the strongest effects. These animals had lower levels of markers associated with inflammatory macrophages, activated hepatic stellate cells and fibrosis.
At the same time, markers of reparative macrophages and mature liver cells increased. Rats receiving the Wnt5a-silenced cells also had higher albumin levels and more proliferating hepatocytes than those receiving cells carrying the empty vector.
The findings suggest that reducing Wnt5a changes how transplanted macrophages behave, allowing them to suppress fibrosis while creating conditions more favourable for liver regeneration.
Advanced liver fibrosis can progress to cirrhosis, liver failure and cancer. Although macrophage-based therapies may support tissue repair, their effects depend heavily on the signals produced by the transplanted cells.
This study identifies Wnt5a as a possible molecular “brake” on the beneficial activity of macrophages. Genetically modifying these cells before transplantation could potentially make cell-based treatment more targeted and effective.
However, the study used an experimentally induced rat model, with only six animals in each group. The cells were also administered alongside a CCR2 inhibitor, making it difficult to separate the contribution of each intervention. Safety, durability and effectiveness in humans remain unknown.
Objective: To observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regenerat…
