TY - JOUR
T1 - Exosomes derived from bone mesenchymal stem cells ameliorate early inflammatory responses following traumatic brain injury
AU - Ni, Haoqi
AU - Yang, Su
AU - Siaw-Debrah, Felix
AU - Hu, Jiangnan
AU - Wu, Ke
AU - He, Zibin
AU - Yang, Jianjing
AU - Pan, Sishi
AU - Lin, Xiao
AU - Ye, Haotuo
AU - Xu, Zhu
AU - Wang, Fan
AU - Jin, Kunlin
AU - Zhuge, Qichuan
AU - Huang, Lijie
N1 - Funding Information:
The work has been supported by National Natural Science Foundation of China (81771262), Zhejiang Health Science and Technology Project (2016RCA022), and Zhejiang Key Research and Development Project (2017C03027).
Publisher Copyright:
Copyright © 2019 Ni, Yang, Siaw-Debrah, Hu, Wu, He, Yang, Pan, Lin, Ye, Xu, Wang, Jin, Zhuge and Huang.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Bone mesenchymal stem cells
KW - Exosomes
KW - Inflammation
KW - Microglia/macrophage
KW - Neuroprotection
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85065481503&partnerID=8YFLogxK
U2 - 10.3389/fnins.2019.00014
DO - 10.3389/fnins.2019.00014
M3 - Article
AN - SCOPUS:85065481503
SN - 1662-4548
VL - 13
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
IS - JAN
M1 - 14
ER -