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

AbstractAIM:
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.
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
Topics
  • 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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