Abstract 133: Transplantation Of Neurosphere-forming Stem Cells Into Circulating Blood Attenuates Acute Inflammatory Activation Of Both Brain And Spleen After Cerebrovascular Ischemic Injury.
Background and Objectives: Transplantation of neural progenitor cells (NPCs) has been studied to achieve the regeneration of damaged brain in experimental stroke models. Tissue ischemia induces systemic inflammatory activation, especially in spleen. However, the interaction between NPCs and immune/inflammatory cells has not been studied in ischemia models. In this study, we investigated whether NPC can attenuate cerebral and systemic inflammatory activation in focal cerebral ischemia.
Methods: Focal cerebral ischemia was induced by intraluminal thread occlusion of the middle cerebral artery for 60 minutes (c57/bl6 adult male mice), and mouse NPC from primary neurosphere (1 million cells) or vehicle (PBS, control group) was injected via tail veins with cerebral reperfusion. Inflammatory cytokines were evaluated with RealTime-PCR at 22 hrs, and the weights of each spleen and thymus were measured.
Results: Cerebral ischemia induced progressive atrophies of spleen and thymus when measured at 22 hr and 96 hr after ischemia. Intravenous injection of NPC accelerated these lymphoid organ atrophies, and the weights of spleen and thymus were significantly lower in NPC-injected mice at 96 hr after the ischemia compared to the vehicle injected mice. RealTime-PCR analysis using ischemic hemispheres and spleens showed reduced expressions of inflammatory cytokines, including TNF-alpha, IL-6, MIP-2, IL-13, FoxP3, IL-1beta, and IP10 in NPC-injected brains and spleens at 22 hr after the ischemia. Transplanted NPCs were detected in systemic organs, and mostly in spleen. NPC-injected mice showed reduced infarct volume and neurologic deficits.
Conclusion: Intravenous transplantation of primary neuro-sphere cells in cerebral ischemia attenuated systemic inflammatory activation, which suggests that the immunomodulating property of neural progenitor cells can be applicable for preventing harmful inflammations after the tissue ischemia.