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

To investigate the effects of mesenchymal stem cells (MSCs) transplantation on rat global cerebral ischemia and the underlying mechanisms.
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.
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.
MSCs transplantation improves functional recovery and reduces inflammatory responses in rats with global cerebral ischemia, maybe via upregulation of TSG-6 expression.
AuthorsQing-ming Lin, Shen Zhao, Li-li Zhou, Xiang-shao Fang, Yue Fu, Zi-tong Huang
JournalActa pharmacologica Sinica (Acta Pharmacol Sin) Vol. 34 Issue 6 Pg. 784-92 (Jun 2013) ISSN: 1745-7254 [Electronic] United States
PMID23474707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cell Adhesion Molecules
  • Inflammation Mediators
  • S100 Calcium Binding Protein beta Subunit
  • Tnfaip6 protein, rat
  • Leukocyte Elastase
  • Animals
  • Blotting, Western
  • Brain Ischemia (physiopathology, therapy)
  • Cell Adhesion Molecules (administration & dosage, genetics, metabolism)
  • Cerebral Cortex (metabolism, pathology)
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Inflammation (pathology, therapy)
  • Inflammation Mediators (metabolism)
  • Injections, Intravenous
  • Leukocyte Elastase (genetics, metabolism)
  • Male
  • Mesenchymal Stem Cell Transplantation (methods)
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • S100 Calcium Binding Protein beta Subunit (blood)
  • Time Factors
  • Treatment Outcome
  • Up-Regulation

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