Magnetotactic Bacteria-Derived Mms6 Gene Helps M2 Macrophages to Form Magnetic Bio-Nanoparticles to Prevent Ferroptosis and Promote Locomotor Functional Recovery after Spinal Cord Injury in Mice

Abstract

Magnetotactic bacteria are microaerobic microorganisms that take up iron from solution and crystallize magnetite nanoparticles called magnetosomes, enclosed by membrane intracellularly and mainly formed by the magnetosome membrane-specific 6 (Mms6) gene. M2 macrophages are transfected by magnetotactic bacteria-derived Mms6 gene to form magnetic bio-nanoparticles. Under myelin debris-rich hypoxic stress in the spinal cord injury (SCI) microenvironment, Mms6-transfected M2 macrophages can antagonize ferroptosis. Meanwhile, transplantation of Mms6-transfected M2 macrophages into SCI mice through intracerebroventricular or intravenous injection can effectively promote structural repair and locomotor functional recovery. As a proof of concept, this study provides a novel strategy in immune cell therapy, which supports the survival and strengthens the function of M2 macrophages based on magnetic bio-nanoparticles which help M2 macrophages to resist ferroptosis. This study also sheds light on this cross-species applications for treating traumatic injury and inflammatory diseases.