Ebersbach, Hilmar, Jascur, Julia, Keshvari, Sahar, Genz, Berit, Teakle, Ngari, Caruso, Melanie, Cestari, Michele F, Patkar, Omkar L, Tse, Brian WC, Sokolowski, Kamil A, MacDonald, Kelly P.A., Miller, Gregory, Ramm, Grant A, Pettit, Allison R, Clouston, Andrew D, Powell, Elizabeth E, Hume, David A and Irvine, Katharine M (2022) Therapeutic potential of macrophage colony-stimulating factor (CSF1) in chronic liver disease. Disease models & mechanisms. ISSN 1754-8411

Abstract

Resident and recruited macrophages control the development and proliferation of the liver. We showed previously in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte proliferation and promoted repair in models of acute hepatic injury in mice. Here we investigated the impact of CSF1-Fc on resolution of advanced fibrosis and liver regeneration, utilizing a non-resolving toxin-induced model of chronic liver injury and fibrosis in C57BL/6J mice. Co-administration of CSF1-Fc with exposure to thioacetamide (TAA) exacerbated inflammation consistent with monocyte contributions to initiation of pathology. After removal of TAA, either acute or chronic CSF1-Fc treatment promoted liver growth, prevented progression and promoted resolution of fibrosis. Acute CSF1-Fc treatment was also anti-fibrotic and pro-regenerative in a model of partial hepatectomy in mice with established fibrosis. The beneficial impacts of CSF1-Fc treatment were associated with monocyte-macrophage recruitment and increased expression of remodeling enzymes and growth factors. These studies indicate that CSF1-dependent macrophages contribute to both initiation and resolution of fibrotic injury and that CSF1-Fc has therapeutic potential in human liver disease.

Item Type:	Article
Date Deposited:	03 Mar 2022 00:45
Last Modified:	03 Mar 2022 00:45
URI:	https://oak.novartis.com/id/eprint/45357