Degree Granting Department
Pathology and Laboratory Medicine
Alison E. Willing, Ph.D.
Samuel Saporta, Ph.D.
Don Cameron, Ph.D.
Thomas W. Klein, Ph.D.
Juan Sanchez-Ramos, PhD, M.D.
MIP-1α, MCP-1, hypoxia, ischemia, stem cell
Previous studies demonstrated that intravenous administration of human umbilical cord blood (HUCB) cells could improve behavioral and neurological recovery of stroked animals following middle cerebral artery occlusion (MCAO). In addition, HUCB cell recipients had less of an inflammatory response with less leukocyte infiltration. In these studies we explored how HUCB cells change the inflammatory response of neurons, astrocytes, and microglia to hypoxia/ischemia. Initiation of the inflammatory response occurs with the expression of chemokines. We determined that monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1alph (MIP-1a), which are upregulated in the brain early after a stroke, induce migration of HUCB cells to the site of injury. Neutralizing these chemokines with antibodies prevented migration in an in vitro migration assay. We next explored the interaction of the whole HUCB mononuclear cell fraction, as well as subpopulations from within the mononuclear fraction (T cell alone, B cell alone, and monocytes/macrophage alone) with cultures of enriched neurons, astrocytes or microglia exposed to hypoxia in an oxygen, glucose deprivation paradigm. We showed that HUCB cells increased the cell viability of neurons and astrocytes, while decreasing cell viability of microglia. There was also a change in the cytokine secretion profile from the cells exposed to HUCB cells under hypoxic conditions. These results suggested that chemokines, MCP-1 and MIP-1a increased in stroked brain, and they played an important role in recruitment of HUCB into the CNS after intravenous administration. Once inside the brain, HUCB could suppress the immune response by promoting microglial death and modulating the function of astrocytes. In addition, HUCB cells provide neuron protection against the injury caused by stroke. However, it is unlikely to contribute the effect of HUCB to a single population of HUCB.
Scholar Commons Citation
Jiang, Lixian, "Interactions of Neurons, Astrocytes and Microglia with HUCB Cell Populations in Stroke Models: Migration, Neuroprotection and Inflammation" (2008). Graduate Theses and Dissertations.