Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) improves brain ischemia-induced pulmonary injury in rats associated to TNF-α expression.

Qin-Qin He,Yu Zou,Yan-Ping Wang,Qing-Jie Xia,Xiang He,Jia Liu,Ting-Hua Wang,Liu-Lin Xiong,Xiao-Song Hu,Chao-Zhi Luo

doi:10.1186/s12993-016-0093-0

Abstract

BackgroundBone marrow mesenchymal stem cell (BMSCs)-based therapy seems to be a promising treatment for acute lung injury, but the therapeutic effects of BMSCs transplantation on acute lung injury induced by brain ischemia and the mechanisms have not been totally elucidated. This study explores the effects of transplantation of BMSCs on acute lung injury induced by focal cerebral ischemia and investigates the underlying mechanism.MethodsAcute lung injury model was induced by middle cerebral artery occlusion (MCAO). BMSCs (with concentration of 1 × 106/ml) were transplanted into host through tail vein 1 day after MCAO. Then, the survival, proliferation and migration of BMSCs in lung were observed at 4 days after transplantation, and histology observation and lung function were assessed for 7 days. Meanwhile, in situ hybridization (ISH), qRT-PCR and western blotting were employed to detect the expression of TNF-α in lung.ResultsNeurobehavioral deficits and acute lung injury could be seen in brain ischemia rats. Implanted BMSCs could survive in the lung, and relieve pulmonary edema, improve lung function, as well as down regulate TNF-α expression.ConclusionsThe grafted BMSCs can survive and migrate widespread in lung and ameliorate lung injury induced by focal cerebral ischemia in the MCAO rat models. The underlying molecular mechanism, at least partially, is related to the suppression of TNF-α.

Highlights

Bone marrow mesenchymal stem cell (BMSCs)-based therapy seems to be a promising treatment for acute lung injury, but the therapeutic effects of BMSCs transplantation on acute lung injury induced by brain ischemia and the mechanisms have not been totally elucidated
We firstly explored whether BMSCs transplantation could alleviate inflammatory activities and improve functional consequence in lung injury induced by brain ischemia, investigated the possible molecular mechanism involving in the expression of TNF-α
Neurologic function evaluation showed that modified neurological severity score (mNSS) score was higher in the brain ischemia group 24 h after middle cerebral artery occlusion (MCAO), as compared with the Sham group (P < 0.05) (Fig. 2c)

Summary

Introduction

Bone marrow mesenchymal stem cell (BMSCs)-based therapy seems to be a promising treatment for acute lung injury, but the therapeutic effects of BMSCs transplantation on acute lung injury induced by brain ischemia and the mechanisms have not been totally elucidated. Pulmonary venues may be α- and β-adrenergic hypersensitive after brain injury This could increase ICP and pulmonary pressures, and induce direct myocyte injuries with wall motion abnormalities [17]. These suggested that vasomotor centers by autonomic nervous system were over-estimated, which could to be an explanation to the association of the edema with central nervous system [18]. Cascade of inflammatory response can cause extravasation of intravascular fluid and the damage of blood vessel walls, which can cause intra-alveolar hemorrhage [21, 22] These observations suggested that a new therapeutic intervention for lung dysfunction is necessary after stroke

Methods

Results

Discussion

Conclusion