Original Article

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

Qing-ming Lin, Shen Zhao, Li-li Zhou, Xiang-shao Fang, Yue Fu, Zi-tong Huang
DOI: 10.1038/aps.2012.199


Qing-ming LIN1, 2, Shen ZHAO1, 2, Li-li ZHOU1, 2, Xiang-shao FANG1, 2, Yue FU1, 2, Zi-tong HUANG1, 2, *
1Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; 2Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou 510120, China

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 5×106 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.

Keywords: mesenchymal stem cells; stem cells transplantation; cardiac arrest; global cerebral ischemia; tumor necrosis factor-α-induced protein 6; inflammation; cytokine; neutrophil elastase

This study was supported in part by a research grant from National Natural Science Foundation of China (81272061) and the Fundamental Research Funds for the Central Universities and Yat-Sen Scholarship for Young Scientists.

We thank Xing-yong CHEN for his assistance with pathological examination.

* To whom correspondence should be addressed.
E-mail huangztdoc@126.com
Received 2012-10-21 Accepted 2012-12-20

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