IMT504 accelerates post-hepatectomy liver regeneration in mice with involvement of GLAST + Wnt1 + bone marrow stromal progenitors

The immunomodulatory oligodeoxynucleotide (ODN) IMT504 exhibits antifibrotic and pro-regenerative properties in the context of liver fibrosis. It also enhances the contribution of GLAST⁺ Wnt1⁺ bone marrow stromal progenitors (BMSPs) to liver regeneration in a mouse model of chronic liver disease. In this study, partial hepatectomy (PHx) was performed in CD1 mice. In parallel, Cre-loxP mice were used to identify GLAST⁺ Wnt1⁺ BMSPs and assess their contribution to liver cells populations. A combination of in vivo and in vitro assays was conducted. IMT504 significantly enhanced liver mass recovery following PHx by promoting both early and late induction of hepatocyte proliferation. The expression dynamics of genes associated with proliferation, liver function, and liver progenitor identity were analyzed. Moreover, IMT504 stimulated the pro-regenerative activity of GLAST⁺ Wnt1⁺ BMSPs by promoting their differentiation into liver cells. In summary, our findings identify IMT504 as a promising therapeutic candidate with strong pro-regenerative potential. Additionally, our data suggest that GLAST⁺ Wnt1⁺ BMSPs represent a unique bone marrow-derived population capable of giving rise to liver cells, further supporting their pro-regenerative role in liver regeneration.