CD11b⁺Ly6G⁺ Myeloid Derived Suppressor Cells Promote Liver Regeneration in a Murine Model of Major Hepatectomy

Liver regeneration depends on sequential activation of pathways and cells involving the
remaining organ in recovery of mass. Proliferation of parenchyma is dependent on
angiogenesis. Understanding liver regeneration associated neovascularization may be
useful for development of clinical interventions. Myeloid Derived Suppressor Cells
(MDSCs) promote tumor angiogenesis, and play a role in developmental processes that
necessitate rapid vascularization. We therefore hypothesized that the MDSCs could play
a role in liver regeneration. Following partial hepatectomy, MDSCs were enriched within
regenerating livers, and their depletion led to increased liver injury and post-operative
mortality, reduced liver weights, decreased hepatic vascularization, reduced hepatocyte
hypertrophy and proliferation, and to aberrant liver function. Gene expression profiling of
regenerating liver-derived MDSCs demonstrated a large-scale transcriptional response,
involving key pathways related to angiogenesis. Functionally, enhanced reactive oxygen
species production and angiogenic capacities of regenerating liver-derived MDSCs were
confirmed. A comparative analysis revealed that the transcriptional response of MDSCs
during liver regeneration resembled that of peripheral blood MDSCs during progression
of abdominal tumors, suggesting a common MDSC gene expression profile promoting
angiogenesis. In conclusion, our study shows that MDSCs contribute to early stages of
liver regeneration possibly by exerting pro-angiogenic functions using a unique
transcriptional program.