Project R-8728

Human and murine macrophages with a stable alternative activation as a therapeutic tool to promote neuroregeneration. (Research)

Worldwide, spinal cord injuries (SCI) are a major cause of morbidity, mortality and reduced quality of life. Until now no regenerative therapy for SCI is available and standard care of SCI patients includes primarily the administration of immunosuppressant drugs and rehabilitation. Thus, new therapeutic strategies are desperately needed. After SCI, pro-inflammatory macrophages dominate the spinal cord and exert detrimental effects by secreting multiple pro-inflammatory factors, by stimulating the formation of the inhibitory fibrotic scar, and by attacking dystrophic axons. Previously, the applicants demonstrated that the implantation of IL-13-expressing mesenchymal stem cells or macrophages induces 'antiinflammatory' arginase-1 (Arg-1)-positive macrophages/microglia in the injured spinal cord, leading to improved functional recovery. Therefore, we investigate here whether high Arg-1 production by macrophages with a stable alternative activation leads to the suppression of pro-inflammatory macrophages/microglia after SCI via arginine depletion. In addition, for translation to the human situation, we will investigate whether Arg1-overexpressing human macrophages exert neuroprotective effects in an in vitro multicellular co-culture model of human stem cell-derived corticospinal-like motor neurons, astrocytes and microglia. Thus, in this project, we aim to analyse one key mechanism of how anti-inflammatory macrophages improve functional recovery after SCI.

01 January 2018 - 31 December 2021