SPP1 macrophages across diseases: A call for reclassification?

SPP1+ macrophages, characterized by elevated expression of the osteopontin gene (secreted phosphoprotein 1, SPP1), have emerged as key players in various pathological contexts, including aging, chronic inflammatory diseases, and cancer. While frequently classified as a subclass of tumor-associated macrophages in oncological settings, their presence in noncancer conditions, such as aging-related disorders and muscular diseases, suggests a broader role beyond tumors. These macrophages share conserved traits, including fibrosis promotion, extracellular matrix remodeling, and immune modulation, often linked to poor clinical outcomes.

Long-term longitudinal study on swine VML model.

Background: Volumetric Muscle Loss (VML), resulting from severe trauma or surgical ablation, is a pathological condition preventing myofibers regeneration, since skeletal muscle owns the remarkable ability to restore tissue damage, but only when limited in size. The current surgical therapies employed in the treatment of this pathology, which particularly affects military personnel, do not yet provide satisfactory results. For this reason, more innovative approaches must be sought, specifically skeletal muscle tissue engineering seems to highlight promising results obtained from preclinical studies in VML mouse model.