Combined effects of hematopoietic progenitor cell mobilization from bone marrow by granulocyte colony stimulating factor and AMD3100 and chemotaxis into the brain using stromal cell-derived factor-1α in an Alzheimer's disease mouse model.

摘要: Transplantation of bone marrow-derived stem cells (BMSCs) has been suggested as a potential therapeutic approach to prevent neurodegenerative diseases, but it remains problematic due issues engraftment, toxicities, and other factors. An alternative strategy is pharmacological-induced recruitment endogenous BMSCs into an injured site by systemic administration growth factors or chemokines. Therefore, the aim this study was examine effects therapy involving granulocyte colony stimulating factor (G-CSF)/AMD3100 (CXCR4 antagonist) stromal cell-derived factor-1α (SDF-1α) on BM-derived hematopoietic progenitor cell (BM-HPC) brain Alzheimer's disease (AD) mouse model. To mobilize BM-HPCs, G-CSF injected intraperitoneally boosted AMD3100. Simultaneously, these mice received intracerebral injection with SDF-1α induce migration mobilized BM-HPCs brain. We found that memory deficit in AD significantly improved treatments, amyloid β deposition unchanged. Interestingly, microglial activation increased microglia neuroprotective phenotype. Furthermore, generating precursor protein/presenilin 1-green fluorescent protein (GFP) chimeric mouse, we ascertained GFP positive identified were BM-derived. Additionally, hippocampal neurogenesis observed receiving combined G-CSF/AMD3100 SDF-1α, not controls animals each treatment alone. These results suggest effective adjuvant inducing G-CSF/AMD3100, two can act synergistically produce effect. This warrants further investigation option for patients future. STEM CELLS 2011;29:1075–1089