Suppression of inflammatory damage to the brain after global cerebral ischemia by transplanted mesenchymal stem cells via secretion of TSG-6
- Author:
Qingming Lin
;
Shirong Lin
;
Yisong Lv
;
Lili Zhou
;
Yue Fu
;
Xiangshao Fang
;
Feng Chen
;
Zitong Huang
- Publication Type:Journal Article
- MeSH:
Heart Arrest;
Mesenchymal Stromal Cells
- From:Neurology Asia
2016;21(2):113-122
- CountryMalaysia
- Language:English
-
Abstract:
Objective: Numerous studies have shown that bone marrow-derived mesenchymal stem cells
(MSCs) enhance neurological recovery after cerebral ischemia. However, the mechanisms are still
not clear. The present study aimed to investigate the beneficial effects of MSCs on global cerebral
ischemia induced by cardiac arrest (CA) and the underlying mechanisms. Methods: Rats subjected to
asphyxial CA were injected intravenously with MSCs (5×106
) at 2 hours after resuscitation. Whole
brain histopathologic damage scores (HDS) were assessed by histopathology at 3 and 7 days after
resuscitation. The distribution of donor MSCs in the brain was evaluated. The expression of tumor
necrosis factor-α-induced protein 6 (TSG-6) and pro-inflammatory cytokines in cerebral cortex was
assayed. After intravenous infusion of TSG-6 siRNA-MSCs, HDS and pro-inflammatory cytokines
were reevaluated at 7 days after resuscitation. Results: Intravenously administered MSCs significantly
reduced whole brain HDS after global cerebral ischemia. Immunofluorescence microscopy revealed
that donor MSCs were primarily found in cerebral cortex and expressed TSG-6. MSCs treatment
significantly increased the expression of TSG-6 and reduced the expression of pro-inflammatory
cytokines in cerebral cortex. In addition, intravenous infusion of TSG-6 siRNA-MSCs failed to
attenuate brain inflammation. Conclusion: Systemically administered MSCs reduced inflammatory
damage to brain in rats with global cerebral ischemia via secretion of TSG-6.