We successfully generated in vitro human regenerative macrophage self-trasplantation (REMaST®) derived from blood monocytes. Transcriptomic analysis of REMaST® confirm the upregulation, compared to M2 macrophages of neurogenic genes, and related to functions required to wound healing including, ECM-remodelling, angiogenesis, response to hypoxia, immune modulation, detoxification and defence, response to stress, and glucose metabolism. Therefore, we decided to exploit REMaST® neuro-regenerative potential and validate these properties. To evaluate REMaST® neurotrophic and neuroprotective activity, we tested REMaST® capability to promote neural sprouting of mouse dorsal root ganglia (mDRG) and human motor neurons (hMN) derived from human induced Pluripotent Stem Cells (iPSCs). Quantification of MAP2 protein showed that REMaST® co-culture resulted in increased neuronal growth (p<0.5). Moreover, we co-cultured neuronal cells with REMaST® in condition of oxygen and glucose deprivation (OGD) and we quantified LDH release through a biochemical colorimetric assay, as a measure of cellular damage. REMaST® were able to statistically significant decrease neuron death (p<0.5). Successively, to test in vitro REMaST® immunomodulatory property, we decided to investigate iNOS expression, typically upregulated during inflammatory reactions, in M1-polarized macrophages both in monoculture and co-cultured with REMaST®. By Flow Cytometry analysis, we found that REMaST® significantly downregulates iNOS expression in M1 macrophages when co-cultured.These data highlight the REMaST® neural regenerative potential. REMaST® may represent a powerful disease-modifying therapy for CNS lesions the potential regenerative effect of on neural tissue.