Spinal cord injury therapies in humans: An overview of current clinical trials and their potential effects on intrinsic CNS macrophages

Introduction: Macrophage activation is a hallmark of spinal cord injury (SCI) pathology. CNS macrophages, derived from resident microglia and blood monocytes, are ubiquitous throughout the injured spinal cord, and respond to signals in the lesion environment by changing their phenotype and function. Depending on their phenotype and activation status, macrophages may initiate secondary injury mechanisms and/or promote CNS regeneration and repair. Areas covered: This review provides a comprehensive overview of current SCI clinical trials that are intended to promote neuroprotection, axon regeneration or cell replacement. None of these potential therapies were developed with the goal of influencing macrophage function; however, it is likely that each will have direct or indirect effects on CNS macrophages. The potential impact of each trial is discussed in the context of CNS macrophage biology. Expert opinion: Activation of CNS macrophages is an inevitable consequence of traumatic SCI. Given that these cells are exquisitely sensitive to changes in microenvironment, any intervention that affects tissue integrity and/or the composition of the cellular milieu will undoubtedly affect CNS macrophages. Thus, it is important to understand how current clinical trials will affect intrinsic CNS macrophages.