New preclinical results support the anti-fibrotic potential of engineered macrophages in multiple fibrosis models:
Engineered TIM4-expressing macrophages correct defective efferocytosis in MASH, demonstrating potent anti-fibrotic activity.
Liver fibrosis is a central late-stage pathway in multiple liver diseases, including MASH, acute liver injury, primary sclerosing cholangitis, primary biliary cholangitis, and others. Treatment options remain limited for advanced liver disease patients. Liver disease is characterized by defective efferocytosis (an anti-inflammatory process by which macrophages clear dead hepatocytes), activation of hepatic stellate cells which leads to collagen accumulation, and chronic inflammation.
New preclinical results demonstrate that macrophages can be genetically engineered to target specific key pathways underlying liver disease with factors including TIM4 (restores efferocytosis), relaxin (inhibits hepatic stellate cell activation), and IL10 (reduces inflammation). Notably, a single dose of macrophages expressing TIM4, alone or together with relaxin, significantly reduced liver fibrosis and hepatic stellate cell activation in the translationally relevant choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) MASH model. The engineered macrophages were well tolerated and outperformed non-engineered cells in all models.
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