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

Haoqi Ni; Su Yang; Felix Siaw-Debrah; Jiangnan Hu; Ke Wu; Zibin He; Jianjing Yang; Sishi Pan; Xiao Lin; Haotuo Ye; Zhu Xu; Fan Wang; Kunlin Jin; Qichuan Zhuge; Lijie Huang

doi:10.3389/fnins.2019.00014

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

Front Neurosci. 2019 Jan 24:13:14. doi: 10.3389/fnins.2019.00014. eCollection 2019.

Authors

Haoqi Ni^{1

2}, Su Yang^{1

2}, Felix Siaw-Debrah^{1

2}, Jiangnan Hu³, Ke Wu^{1

2}, Zibin He^{1

2}, Jianjing Yang^{1

2}, Sishi Pan^{1

2}, Xiao Lin^{1

2}, Haotuo Ye^{1

2}, Zhu Xu^{1

2}, Fan Wang^{1

2}, Kunlin Jin^{1

3}, Qichuan Zhuge^{1

2}, Lijie Huang^{1

2}

Affiliations

¹ Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, United States.

Abstract

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 μg protein of BMSCs-exosomes 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-α (TNF-α) and interleukin (IL)-1β, while enhancing the expression of the anti-apoptosis protein B-cell lymphoma 2 (BCL-2). 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.

Keywords: bone mesenchymal stem cells; exosomes; inflammation; microglia/macrophage; neuroprotection; traumatic brain injury.