Mesenchymal stem cells transplantation suppresses inflammatory responses in global cerebral ischemia: contribution of TNF-α-induced protein 6

• Published in: Acta pharmacologica Sinica Vol. 34; no. 6; pp. 784 - 792
• Main Authors: Lin, Qing-ming, Zhao, Shen, Zhou, Li-li, Fang, Xiang-shao, Fu, Yue, Huang, Zi-tong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2013; Nature Publishing Group
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Brain Ischemia - physiopathology; Brain Ischemia - therapy; Cell Adhesion Molecules - administration & dosage; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Immunology; Inflammation - pathology; Inflammation - therapy; Inflammation Mediators - metabolism; Injections, Intravenous; Internal Medicine; Leukocyte Elastase - genetics; Leukocyte Elastase - metabolism; Male; Medical Microbiology; Mesenchymal Stem Cell Transplantation - methods; Original; original-article; Pharmacology/Toxicology; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; S100 Calcium Binding Protein beta Subunit - blood; Time Factors; Treatment Outcome; Up-Regulation; Vaccine; cytokine; global cerebral ischemia; inflammation; mesenchymal stem cells; neutrophil elastase; tumor necrosis factor-α-induced protein 6; cardiac arrest; stem cells transplantation
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2012.199

Aim: To investigate the effects of mesenchymal stem cells (MSCs) transplantation on rat global cerebral ischemia and the underlying mechanisms. Methods: Adult male SD rats underwent asphxial cardiac arrest to induce global cerebral ischemia, then received intravenous injection of 5×10 6 cultured MSCs of SD rats at 2 h after resuscitation. In another group of cardiac arrest rats, tumor necrosis factor-α-induced protein 6 (TSG-6, 6 μg) was injected into the right lateral ventricle. Functional outcome was assessed at 1, 3, and 7 d after resuscitation. Donor MSCs in the brains were detected at 3 d after resuscitation. The level of serum S-100B and proinflammatory cytokines in cerebral cortex were assayed using ELISA. The expression of TSG-6 and proinflammatory cytokines in cerebral cortex was assayed using RT-PCR. Western blot was performed to determine the levels of TSG-6 and neutrophil elastase in cerebral cortex. Results: MSCs transplantation significantly reduced serum S-100B level, and improved neurological function after global cerebral ischemia compared to the PBS-treated group. The MSCs injected migrated into the ischemic brains, and were observed mainly in the cerebral cortex. Furthermore, MSCs transplantation significantly increased the expression of TSG-6, and reduced the expression of neutrophil elastase and proinflammatory cytokines in the cerebral cortex. Intracerebroventricular injection of TSG-6 reproduced the beneficial effects of MSCs transplantation in rats with global cerebral ischemia. Conclusion: MSCs transplantation improves functional recovery and reduces inflammatory responses in rats with global cerebral ischemia, maybe via upregulation of TSG-6 expression.