Exosomes Derived From Bone Mesenchymal Stem Cells Ameliorate Early Inflammatory Responses Following Traumatic Brain Injury

被引：177

作者：

Ni, Haoqi ^{[1
,2
]}

Yang, Su ^{[1
,2
]}

Siaw-Debrah, Felix ^{[1
,2
]}

Hu, Jiangnan ^{[3
]}

Wu, Ke ^{[1
,2
]}

He, Zibin ^{[1
,2
]}

Yang, Jianjing ^{[1
,2
]}

Pan, Sishi ^{[1
,2
]}

Lin, Xiao ^{[1
,2
]}

Ye, Haotuo ^{[1
,2
]}

Xu, Zhu ^{[1
,2
]}

Wang, Fan ^{[1
,2
]}

Jin, Kunlin ^{[1
,3
]}

Zhuge, Qichuan ^{[1
,2
]}

Huang, Lijie ^{[1
,2
]}

机构：

[1] Wenzhou Med Univ, Affiliated Hosp 1, Zhejiang Prov Key Lab Aging & Neurol Disorder Res, Wenzhou, Peoples R China

[2] Wenzhou Med Univ, Affiliated Hosp 1, Dept Neurosurg, Wenzhou, Peoples R China

[3] Univ North Texas, Dept Pharmacol & Neurosci, Hlth Sci Ctr, Ft Worth, TX USA

来源：

FRONTIERS IN NEUROSCIENCE | 2019年 / 13卷

基金：

中国国家自然科学基金;

关键词：

traumatic brain injury; bone mesenchymal stem cells; exosomes; neuroprotection; microglia/macrophage; inflammation; STROMAL CELLS; EXTRACELLULAR VESICLES; FUNCTIONAL RECOVERY; ANIMAL-MODELS; TRANSPLANTATION; REGULATORS; THERAPY;

D O I：

10.3389/fnins.2019.00014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. Although treatment guidelines have been developed, no best treatment option or medicine for this condition exists. Recently, mesenchymal stem cells (MSCs)-derived exosomes have shown lots of promise for the treatment of brain disorders, with some results highlighting the neuroprotective effects through neurogenesis and angiogenesis after TBI. However, studies focusing on the role of exosomes in the early stages of neuroinflammation post-TBI are not sufficient. In this study, we investigated the role of bone mesenchymal stem cells (BMSCs)-exosomes in attenuating neuroinflammation at an early stage post-TBI and explored the potential regulatory neuroprotective mechanism. We administered 30 vg protein of BMSCsexosomes or an equal volume of phosphate-buffered saline (PBS) via the retro-orbital route into C57BL/6 male mice 15 min after controlled cortical impact (CCI)-induced TBI. The results showed that the administration of BMSCs-exosomes reduced the lesion size and improved the neurobehavioral performance assessed by modified Neurological Severity Score (mNSS) and rotarod test. In addition, BMSCs-exosomes inhibited the expression of proapoptosis protein Bcl-2-associated X protein (BAX) and proinflammation cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta, while enhancing the expression of the anti-apoptosis protein B-cell lymphoma 2 (BCL2). Furthermore, BMSCs-exosomes modulated microglia/macrophage polarization by downregulating the expression of inducible nitric oxide synthase (INOS) and upregulating the expression of clusters of differentiation 206 (CD206) and arginase-1 (Arg1). In summary, our result shows that BMSCs-exosomes serve a neuroprotective function by inhibiting early neuroinflammation in TBI mice through modulating the polarization of microglia/macrophages. Further research into this may serve as a potential therapeutic strategy for the future treatment of TBI.

引用

页数：10

共 46 条

[21] M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination [J].