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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number14
JournalFrontiers in Neuroscience
Volume13
Issue numberJAN
DOIs
StatePublished - 1 Jan 2019

Fingerprint

Exosomes
Mesenchymal Stromal Cells
Bone and Bones
Microglia
Macrophages
Rotarod Performance Test
Arginase
bcl-2-Associated X Protein
Traumatic Brain Injury
Neurogenesis
Brain Diseases
Neuroprotective Agents
B-Cell Lymphoma
Nitric Oxide Synthase Type II
Interleukin-1
Proteins
Down-Regulation
Tumor Necrosis Factor-alpha
Phosphates
Medicine

Keywords

  • Bone mesenchymal stem cells
  • Exosomes
  • Inflammation
  • Microglia/macrophage
  • Neuroprotection
  • Traumatic brain injury

Cite this

Ni, Haoqi ; Yang, Su ; Siaw-Debrah, Felix ; Hu, Jiangnan ; Wu, Ke ; He, Zibin ; Yang, Jianjing ; Pan, Sishi ; Lin, Xiao ; Ye, Haotuo ; Xu, Zhu ; Wang, Fan ; Jin, Kunlin ; Zhuge, Qichuan ; Huang, Lijie. / Exosomes derived from bone mesenchymal stem cells ameliorate early inflammatory responses following traumatic brain injury. In: Frontiers in Neuroscience. 2019 ; Vol. 13, No. JAN.
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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.",
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author = "Haoqi Ni and Su Yang and Felix Siaw-Debrah and Jiangnan Hu and Ke Wu and Zibin He and Jianjing Yang and Sishi Pan and Xiao Lin and Haotuo Ye and Zhu Xu and Fan Wang and Kunlin Jin and Qichuan Zhuge and Lijie Huang",
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Ni, H, Yang, S, Siaw-Debrah, F, Hu, J, Wu, K, He, Z, Yang, J, Pan, S, Lin, X, Ye, H, Xu, Z, Wang, F, Jin, K, Zhuge, Q & Huang, L 2019, 'Exosomes derived from bone mesenchymal stem cells ameliorate early inflammatory responses following traumatic brain injury', Frontiers in Neuroscience, vol. 13, no. JAN, 14. https://doi.org/10.3389/fnins.2019.00014

Exosomes derived from bone mesenchymal stem cells ameliorate early inflammatory responses following traumatic brain injury. / Ni, Haoqi; Yang, Su; Siaw-Debrah, Felix; Hu, Jiangnan; Wu, Ke; He, Zibin; Yang, Jianjing; Pan, Sishi; Lin, Xiao; Ye, Haotuo; Xu, Zhu; Wang, Fan; Jin, Kunlin; Zhuge, Qichuan; Huang, Lijie.

In: Frontiers in Neuroscience, Vol. 13, No. JAN, 14, 01.01.2019.

Research output: Contribution to journalArticle

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

PY - 2019/1/1

Y1 - 2019/1/1

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

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