Poster abstracts
Poster number 90 submitted by Randall Carpenter
Human immune cells infiltrate the lesion of humanized mice after contusive spinal cord injury
Randall S. Carpenter (Neuroscience Graduate Program, The Ohio State University, Columbus, OH), Kristina A. Kigerl (Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, OH), Stefan Niewiesk (Department of Veterinary Biosciences, The Ohio State University, Columbus, OH), Phillip G. Popovich (Center for Brain and Spinal Cord Repair, Department of Neuroscience, The Ohio State University, Columbus, OH)
Abstract:
Mice are important pre-clinical models for investigating inflammation and immune system function after acute spinal cord injury (SCI). However, recent data indicate that the composition and function of mouse and human immune systems differ. Understanding the human immune response to SCI and the development of novel immune modulatory therapies may benefit from the generation of animal models that better reflect the human condition. Humanized mice are immunocompromised mice engrafted with human blood stem cells, resulting in the development of a human immune system. The purpose of the current study was to determine if humanized mice can be used to investigate human immune responses to acute SCI. Newborn NOD-SCID-IL2rg null (NSG) mice underwent mild irradiation followed by injection of 50K human CD34+ hematopoietic stem cells into the liver. Ten weeks after engraftment human immune cells made up 8% of all peripheral white blood cells in humanized NSG (hNSG) mice. Thirteen weeks after engraftment hNSG mice were subjected to a moderate thoracic spinal cord contusion injury. After SCI, the proportion of human immune cells increased significantly to 57%, likely due post-injury changes in hematopoiesis. Also, human T cells, B cells, and macrophages were identified in peripheral organs. Human immune cells infiltrated the spinal cord by 28 dpi and were confined to the lesion core, internal to the glial scar. The composition of human immune cells in the lesion included human macrophages, T cells, and B cells. Human macrophages displayed a large, phagocytic phenotype and were the most abundant human immune cell in the lesion. Human T cells were interspersed among phagocytic macrophages, occasionally forming small clusters within and surrounding the lesion. Human B cells in the lesion were rare, and could only be identified in a subset of hNSG mice. These results indicate that humanized mouse models can be utilized to investigate human neuroinflammation after SCI.
Keywords: Neurotrauma, Humanized Mice, Neuroimmunology