Intravenously Infusing the Secretome of Adipose-Derived Mesenchymal Stem Cells Ameliorates Neuroinflammation and Neurological Functioning After Traumatic Brain Injury

被引:50
作者
Xu, Chao [1 ,2 ]
Diao, Yun-Feng [2 ]
Wang, Jing [2 ,3 ]
Liang, Jun [1 ]
Xu, Hai-Huan [1 ,2 ]
Zhao, Ming-Liang [2 ]
Zheng, Bin [1 ]
Luan, Zuo [4 ]
Wang, Jing-Jing [2 ]
Yang, Xi-Ping [2 ]
Wei, Meng-Guang [2 ]
Duan, Jing-Hao [1 ]
Wang, Ke-Qiang [1 ]
Chen, Chong [1 ,2 ]
Chen, Feng [2 ]
Ming, Dong [1 ]
Zhang, Sai [2 ]
Sun, Hong-Tao [2 ]
Li, Xiao-Hong [1 ]
机构
[1] Tianjin Univ, Acad Med Engn & Translat Med, Tianjin 300072, Peoples R China
[2] Characterist Med Ctr PAPF, Inst Traumat Brain Injury & Neurol, 220 Chenglin Rd, Tianjin 300162, Peoples R China
[3] Shanxi Dayi Hosp, Dept Neurosurg, Taiyuan, Peoples R China
[4] Navy Gen Hosp, Dept Pediat, Pediat Surg, Beijing, Peoples R China
关键词
traumatic brain injury; secretome; neuroinflammation; the polarization of microglia; neurological function; MACROPHAGES; EDEMA; NEUROPROTECTION; INFLAMMATION; POLARIZATION; MICROGLIA; MODULATE; STROKE; RATS;
D O I
10.1089/scd.2019.0173
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The secretome of mesenchymal stem cell (MSC) offers a series of immunoregulatory properties and is regarded as an effective method of mitigating secondary neuroinflammation induced by traumatic brain injury (TBI). The secretome of adipose-derived MSCs (ASC-ST) was collected under hypoxia conditions. Proteomics data were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and concentrations of major components were tested. After the TBI caused by an electric cortical contusion impactor, rats were injected ASC-ST through caudal veins for 7 days. The neurological functional prognosis of TBI rats was significantly improved, and the vasogenic edema of brain tissues that was measured 14 days after TBI was relieved by ASC-ST, corresponding to brain water content levels. ASC-ST ameliorated TBI-induced neuroinflammatory environments that caused the edema, the apoptosis of the neural cells, and the nerve fiber damage by increasing the number of M2 phenotypes present while reducing the number of M1 phenotype microglia present. Furthermore, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels were reduced, whereas transforming growth factor-beta (TGF-beta) and tumor necrosis factor-stimulated gene 6 protein (TSG-6) levels were increased after secretome treatment. Altogether, ASC-ST is capable of improving neural functioning by modulating TBI-induced neuroinflammation and its related secondary insults. ASC-ST may be one of the most promising candidates for regulating the secondary inflammatory reactions of central nervous systems for clinical use.
引用
收藏
页码:222 / 234
页数:13
相关论文
共 44 条
[1]   Mortality and long-term functional outcome associated with intracranial pressure after traumatic brain injury [J].
Badri, Shide ;
Chen, Jasper ;
Barber, Jason ;
Temkin, Nancy R. ;
Dikmen, Sureyya S. ;
Chesnut, Randall M. ;
Deem, Steven ;
Yanez, N. David ;
Treggiari, Miriam M. .
INTENSIVE CARE MEDICINE, 2012, 38 (11) :1800-1809
[2]   Dynamic Compaction of Human Mesenchymal Stem/Precursor Cells into Spheres Self-Activates Caspase-Dependent IL1 Signaling to Enhance Secretion of Modulators of Inflammation and Immunity (PGE2, TSG6, and STC1) [J].
Bartosh, Thomas J. ;
Yloestalo, Joni H. ;
Bazhanov, Nikolay ;
Kuhlman, Jessica ;
Prockop, Darwin J. .
STEM CELLS, 2013, 31 (11) :2443-2456
[3]   Emboli formation rather than inflammatory mediators are responsible for increased cerebral water content after conventional and assisted beating-heart myocardial revascularization in a porcine model [J].
Bierbach, Benjamin ;
Meier, Matthias ;
Kasper-Koenig, Walter ;
Heimann, Axel ;
Alessandri, Beat ;
Horstick, Georg ;
Oelert, Hellmut ;
Kempski, Oliver .
STROKE, 2008, 39 (01) :213-219
[4]   Neuroinflammation in animal models of traumatic brain injury [J].
Chiu, Chong-Chi ;
Liao, Yi-En ;
Yang, Ling-Yu ;
Wang, Jing-Ya ;
Tweedie, David ;
Karnati, Hanuma K. ;
Greig, Nigel H. ;
Wang, Jia-Yi .
JOURNAL OF NEUROSCIENCE METHODS, 2016, 272 :38-49
[5]   Intranasal Delivery of Bone Marrow-Derived Mesenchymal Stem Cells, Macrophages, and Microglia to the Brain in Mouse Models of Alzheimer's and Parkinson's Disease [J].
Danielyan, Lusine ;
Beer-Hammer, Sandra ;
Stolzing, Alexandra ;
Schaefer, Richard ;
Siegel, Georg ;
Fabian, Claire ;
Kahle, Philipp ;
Biedermann, Tilo ;
Lourhmati, Ali ;
Buadze, Marine ;
Novakovic, Ana ;
Proksch, Barbara ;
Gleiter, Christoph H. ;
Frey, William H., II ;
Schwab, Matthias .
CELL TRANSPLANTATION, 2014, 23 :S123-S139
[6]   Macrophages modulate the viability and growth of human mesenchymal stem cells [J].
Freytes, Donald O. ;
Kang, Jung W. ;
Marcos-Campos, Ivan ;
Vunjak-Novakovic, Gordana .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2013, 114 (01) :220-229
[7]   Proinflammatory cytokine regulation of cyclic AMP-phosphodiesterase 4 signaling in microglia in vitro and following CNS injury [J].
Ghosh, Mousumi ;
Garcia-Castillo, Daniela ;
Aguirre, Vladimir ;
Golshani, Roozbeh ;
Atkins, Coleen M. ;
Bramlett, Helen M. ;
Dietrich, W. Dalton ;
Pearse, Damien D. .
GLIA, 2012, 60 (12) :1839-1859
[8]   Therapies negating neuroinflammation after brain trauma [J].
Hellewell, Sarah ;
Semple, Bridgette D. ;
Morganti-Kossmann, Maria Cristina .
BRAIN RESEARCH, 2016, 1640 :36-56
[9]   Clinical evidence of inflammation driving secondary brain injury: A systematic review [J].
Hinson, Holly E. ;
Rowell, Susan ;
Schreiber, Martin .
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY, 2015, 78 (01) :184-191
[10]   Mesenchymal Stem Cell-Conditioned Medium Triggers Neuroinflammation and Reactive Species Generation in Organotypic Cultures of Rat Hippocampus [J].
Horn, Ana Paula ;
Bernardi, Andressa ;
Frozza, Rudimar Luiz ;
Grudzinski, Patricia Bencke ;
Hoppe, Juliana Bender ;
de Souza, Luiz Fernando ;
Chagastelles, Pedro ;
de Souza Wyse, Angela Terezinha ;
Bernard, Elena Aida ;
Oliveira Battastini, Ana Maria ;
Campos, Maria Martha ;
Lenz, Guido ;
Nardi, Nance Beyer ;
Salbego, Christianne .
STEM CELLS AND DEVELOPMENT, 2011, 20 (07) :1171-1181