Hematopoietic dysfunction and immune suppression after spinal cord injury

Ohio State University, Columbus OH

Investigators

Linked publications, trials & patents

Abstract

Project Summary (Abstract) Clinical and experimental data indicate that immune system function is impaired after SCI; however, the mechanisms underlying post-injury immune dysfunction are incompletely understood. Given that immune cells are born in generative lymphoid tissues (e.g., bone marrow), it is likely that SCI adversely affects hematopoiesis, i.e., the process of forming functional blood and immune cells from hematopoietic stem and progenitor cells (HSPCs) in bone marrow. There is little data on this topic although two clinical studies support the hypothesis that deficits in hematopoiesis are causal in post-injury immune suppression. The goal of this proposal is to use a mouse model to determine if and how SCI adversely affects hematopoiesis and how this contributes to immune suppression. We hypothesize that high-level SCI will cause hematopoietic dysfunction by altering normal sympathetic activity to the bone marrow hematopoietic niche and that this will contribute to immune suppression. Experiments in Aim 1 will define the spatiotemporal dynamics of hematopoiesis and also evaluate HSPC function at acute and chronic time points after SCI. These data will be the first to define hematopoiesis and/or hematopoietic dysfunction in an experimental model of SCI. Even if SCI reduces numbers or function of HSPCs, some stem/precursor cells will undoubtedly persist in the bone marrow. Experiments in Aim 2 will introduce an inflammatory stimulus to ?challenge? these residual cells in the hematopoietic niche and reveal whether post-injury immune suppression is caused by an impaired ability to stimulate HSPC mobilization, survival and differentiation. Together, data from this proposal will provide the first comprehensive analysis of acute and chronic post-SCI changes in hematopoiesis. Such data could provide novel insight needed to develop therapies capable of modulating hematopoiesis and immune function to improve the quality of life for SCI patients.