Exosomes derived from bone marrow mesenchymal stem cells overexpressing microRNA-25 protect spinal cords against transient ischemia

The Journal of Thoracic and Cardiovascular Surgery

Jiang Shi¹  Linlin Zhao²  Xiaojing Jiang³ 

[1] Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, China;Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China;Department of Cardiac Surgery, the People's Hospital of Liaoning Province, Shenyang, China

关键词: spinal cord;    ischemia;    mesenchymal stem cells;    exosome;    microRNA;   

DOI  :  10.1016/j.jtcvs.2018.07.095

学科分类：心脏病和心血管学

来源: Mosby, Inc.

【 摘 要 】

ObjectiveWe investigated the neuroprotection of exosomes derived from bone marrow mesenchymal stem cells overexpressing microRNA-25 on ischemic spinal cords.MethodsCultured mesenchymal stem cells were transfected with lentivirus vectors containing pre–microRNA-25 or control vectors. Exosomes were isolated and harvested by centrifugation. Spinal cord ischemia was induced in rats by crossclamping the descending aorta just distal to the left subclavian artery for 15 minutes. Exosomes from mesenchymal stem cells, mesenchymal stem cells transfected with control vector, or pre–microRNA-25 were administered by intrathecal injection before ischemia. Hind-limb motor function was assessed with the motor deficit index. Contents of interleukin-1β, tumor necrosis factor-α, malondialdehyde, and superoxide dismutase activity were measured using commercial kits. Expressions of NADPH oxidase 2, NADPH oxidase 4, and microRNA-25 were detected by Western blot and quantitative reverse transcription polymerase chain reaction. Lumbar spinal cords were harvested for histologic examination.ResultsTransfection of pre–microRNA-25 significantly enhanced microRNA-25 levels in mesenchymal stem cells and their exosomes (P P P P P P = .012), but not NADPH oxidase 2 expression, decreased malondialdehyde content (P = .022), increased superoxide dismutase activity (P P P = .002).ConclusionsThe neuroprotection of exosomes from mesenchymal stem cells on ischemic spinal cords can be enhanced by genetic modification of the exosomes to contain elevated microRNA-25.

【 授权许可】

Unknown