1. Hypoxic conditioned medium derived from bone marrow mesenchymal stromal cells protects against ischemic stroke in rats.
- Author
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Jiang RH, Wu CJ, Xu XQ, Lu SS, Zu QQ, Zhao LB, Wang J, Liu S, and Shi HB
- Subjects
- Animals, Apoptosis drug effects, Brain metabolism, Brain pathology, Brain physiopathology, Cell Hypoxia, Cells, Cultured, Culture Media, Conditioned metabolism, Cytokines metabolism, Disease Models, Animal, Infarction, Middle Cerebral Artery metabolism, Infarction, Middle Cerebral Artery pathology, Infarction, Middle Cerebral Artery physiopathology, Male, Neovascularization, Physiologic drug effects, Neuroprotective Agents metabolism, Phosphatidylinositol 3-Kinase metabolism, Phosphorylation, Proto-Oncogene Proteins c-akt metabolism, Rats, Sprague-Dawley, Recovery of Function, Bone Marrow Cells metabolism, Brain drug effects, Culture Media, Conditioned pharmacology, Infarction, Middle Cerebral Artery drug therapy, Mesenchymal Stem Cells metabolism, Neuroprotective Agents pharmacology
- Abstract
In recent years, studies have shown that the secretome of bone marrow mesenchymal stromal cells (BMSCs) contains many growth factors, cytokines, and antioxidants, which may provide novel approaches to treat ischemic diseases. Furthermore, the secretome may be modulated by hypoxic preconditioning. We hypothesized that conditioned medium (CM) derived from BMSCs plays a crucial role in reducing tissue damage and improving neurological recovery after ischemic stroke and that hypoxic preconditioning of BMSCs robustly improves these activities. Rats were subjected to ischemic stroke by middle cerebral artery occlusion and then intravenously administered hypoxic CM, normoxic CM, or Dulbecco modified Eagle medium (DMEM, control). Cytokine antibody arrays and label-free quantitative proteomics analysis were used to compare the differences between hypoxic CM and normoxic CM. Injection of normoxic CM significantly reduced the infarct area and improved neurological recovery after stroke compared with administering DMEM. These outcomes may be associated with the attenuation of apoptosis and promotion of angiogenesis. Hypoxic preconditioning significantly enhanced these therapeutic effects. Fourteen proteins were significantly increased in hypoxic CM compared with normoxic CM as measured by cytokine arrays. The label-free quantitative proteomics analysis revealed 163 proteins that were differentially expressed between the two groups, including 107 upregulated proteins and 56 downregulated proteins. Collectively, our results demonstrate that hypoxic CM protected brain tissue from ischemic injury and promoted functional recovery after stroke in rats and that hypoxic CM may be the basis of a potential therapy for stroke patients., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2019
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