Spinal Cord Injury (SCI) is a dramatic and irreversible event that leads to the loss of motor and/or sensory functions. After complete SCI, such as grade ASIA-A lesions, the neural tissue fails to repair causing permanent neurological deficits. Nowadays, complete SCI represents an unmet medical need, with no treatments capable to reduce cell death, heal the neural parenchyma, and promote axonal regrowth. In this work, we have identified a set of tumor-associated macrophages with neurogenic properties opening the prospective for a new effective cell therapy for neural degeneration diseases. We therefore have established a method to obtained macrophages REMaST® with specific neurogenic activities. We tested REMaST® regenerative potential in a pre-clinical model of severe contusive SCI which reproduces biological and clinical features of grade ASIA-A human SCI. We found that adoptive transfer of REMaST® in severe SCI mice significantly improved motor recovery. By using a complementary set of refractive X-ray computed tomography, histological, and proteomic evaluations, we identified multiple REMaST® mechanisms of action including the promotion of neuronal survival and axonal regrowth, angiogenesis and tissue oxygenation, cyst and ECM-remodeling, and reduction of chronic inflammation. At molecular level REMaST® therapeutic effect was mediated by RICTOR signalling pathway. Of note, we found similar exclusive neural regenerative property also in human REMaST® derived from blood monocytes. Collectively, these data showed that REMaST® are a multitarget disease-modifier for severe SCI, and they may be a novel autologous immune cell therapy exploitable for neural tissue regeneration.