- 作者: Yongwei Yao; Fumin Zhang; Liansheng Wang; Guohui Zhang; Zhaojun Wang; Jianmei Chen; Xiang Gao
- 作者服務機構: Department of Cardiology ,First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
- 中文摘要: --
- 英文摘要:
Background :
Mesenchymal stem cells (MSCs)-based regenerative therapy is currently regarded as
an alternative approach to salvage the acute myocardial infarcted hearts. However, the
efficiency of MSCs transplantation is limited by lower survival rate of engrafted
MSCs. In previous study, we found that 1.0 μg/ml Lipopolysaccharide (LPS) could
protect MSCs against apoptosis induced by oxidative stress and meanwhile enhance
the proliferation of MSCs. Therefore, in the present study, we firstly preconditioned
MSCs with 1.0 μg/ml LPS, then transplanted MSCs into ischemic myocardium, and
observed the survival and cardiac protective capacity of MSCs in a rat model of acute
myocardial infarction. Furthermore, we tried to explore the underlying mechanisms
and the role of Toll-like receptor-4 (TLR4) in the signal pathway of LPS-induced
cardiac protection.
Methods and results : Acute myocardial infarction model was developed by left anterior descending
coronary artery ligation. 60 rats were divided into 4 groups randomly and given an
intramyocardial injection of one of the following treatments: 30μl PBS (control
group), 3×106 wild MSCs/30μl (wMSCs group), 3×106 LPS-preconditioned wild
MSCs/30μl (LPS-wMSCs group),or 3×106 LPS- preconditioned TLR4 gene deleted
MSCs/30μl (LPS-tMSCs group). After 3 weeks, LPS-preconditioned wild MSCs
transplantation ameliorated cardiac function and reduced fibrosis of infarcted
myocardium. Vascular density was markedly increased in LPS-wMSCs group compared with other three groups. Survival rate of engrafted MSCs was elevated and
apoptosis of myocardium was reduced in infarcted heart. Expression of vascular
endothelial growth factor (VEGF) and phospho-Akt was increased in the infarcted
myocardium after transplantation of LPS- preconditioned MSCs.
Conclusions :
LPS preconditioning enhanced survival of engrafted MSCs, stimulated expression of
VEGF and activated PI3K/Akt pathway. LPS preconditioning before MSCs
transplantation resulted in superior therapeutic neovascularization and recovery of
cardiac function. LPS preconditioning provided a novel strategy in maximizing
biologic and functional properties of MSCs. - 中文關鍵字: --
- 英文關鍵字: --