Peripheral Transplantation of Mesenchymal Stem Cells at Sepsis Convalescence Improves Cognitive Function of Sepsis Surviving Mice

OBJECTIVE: To investigate the effects of peripheral transplantation of mesenchymal stem cells (MSCs) at sepsis convalescence on post-sepsis cognitive function and underlying mechanisms in mice. METHODS: Sepsis was induced by cecal ligation and puncture (CLP) in mice. Bone marrow-derived MSCs from mice were cultured and injected via tail vein on the 8(th) day after CLP. Cognitive function was detected in open field, novel object recognition task, and delayed matching-to-place water maze task during 10-26 days after CLP. Neuroinflammation, neurogenesis, and peripheral inflammation were detected on the 12(th) and 31(th) days after CLP. MSCs tracing was detected during 8-10 days after CLP. RESULTS: Transplanted MSCs were located at peripheral organs (lung, spleen, liver) and had no obvious effects on survival and weight of sepsis mice. Transplanted MSCs mitigated cognitive impairments and hippocampal microglial activation, improved hippocampal neurogenesis of sepsis surviving mice, and had no obvious effect on the leukocyte amount, the neutrophil percentage, and the inflammatory factors of peripheral blood, and the hippocampal inflammatory factors. CONCLUSIONS: Our data indicated that MSCs transplantation via peripheral vein at later phase of sepsis can improve post-sepsis cognitive impairment and hippocampal neurogenesis of sepsis surviving mice.