Effects of local administration of allogenic adipose tissue-derived mesenchymal stem cells on functional recovery in experimental traumatic brain injury

Brain Injury ◽  
2015 ◽  
Vol 29 (12) ◽  
pp. 1497-1510 ◽  
Author(s):  
Ignacio Mastro-Martínez ◽  
Esther Pérez-Suárez ◽  
Gustavo Melen ◽  
África González-Murillo ◽  
Fernando Casco ◽  
...  
2019 ◽  
Vol 28 (7) ◽  
pp. 874-884 ◽  
Author(s):  
Hui Ma ◽  
Ping Kuen Lam ◽  
Cindy See Wai Tong ◽  
Kin Ki Yan Lo ◽  
George Kwok Chu Wong ◽  
...  

Traumatic brain injury is one of the leading causes of mortality and morbidity worldwide. At present there is no effective treatment. Previous studies have demonstrated that topical application of adipose tissue-derived mesenchymal stem cells can improve functional recovery in experimental traumatic brain injury. In this study, we evaluated whether hypoxic preconditioned mesenchymal stem cells could enhance the recovery from traumatic brain injury. Traumatic brain injury was induced with an electromagnetically controlled cortical impact device. Two million mesenchymal stem cells derived from the adipose tissue of transgenic green fluorescent protein Sprague-Dawley rats were cultured under either hypoxic (2.5% O2 for 18 hours) ( N = 30) or normoxic (18% O2) ( N = 30) conditions, then topically applied to the exposed cerebral cortex within 1 hour after traumatic brain injury. A thin layer of fibrin was used to fix the cells in position. No treatment was given to the animals with traumatic brain injury ( N = 30). Animals that underwent craniectomy without traumatic brain injury were treated as the sham group ( N = 15). Neurological functions were evaluated with water maze, Roto-rod and gait analysis. Animals were sacrificed at days 3, 7, and 14 for microscopic examinations and real-time polymerase chain reaction analysis. The rats treated with hypoxic mesenchymal stem cells showed the greatest improvement in neurological function recovery. More green fluorescent protein-positive cells were found in the injured brain parenchyma treated with hypoxic mesenchymal stem cells that co-expressed glial fibrillary acidic protein, Nestin, and NeuN. Moreover, there was early astrocytosis triggered by the infiltration of more glial fibrillary acidic protein-positive cells and microgliosis was suppressed with fewer ionized calcium binding adapter molecule 1-positive cells in the penumbra region of hypoxic mesenchymal stem cells group at day 3. Compared with normoxic mesenchymal stem cells and traumatic brain injury only groups, there was significantly ( p < 0.05) less neuronal death in both the hippocampus and penumbral regions in sections treated with hypoxic mesenchymal stem cells as determined by Cresyl violet and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining respectively. The expression of pro-inflammatory genes (interleukin 6, interleukin 1a, interleukin 1b, tumor necrosis factor α) was upregulated and apoptotic gene (Caspase-3) expression was suppressed at day 3. Anti-inflammatory (interleukin 10) and anti-apoptotic (BCL2 associated agonist of cell death) gene expression was upregulated at days 7 and 14. Our study showed that a hypoxic precondition enhanced the beneficial effects of mesenchymal stem cells on neurological recovery after traumatic brain injury.


Stem Cells ◽  
2017 ◽  
Vol 35 (5) ◽  
pp. 1416-1430 ◽  
Author(s):  
Daniel J. Kota ◽  
Karthik S. Prabhakara ◽  
Naama Toledano-Furman ◽  
Deepa Bhattarai ◽  
Qingzheng Chen ◽  
...  

2021 ◽  
Author(s):  
Qiaozhen Qin ◽  
Ting Wang ◽  
Zhenhua Xu ◽  
Shuirong Liu ◽  
Heyang Zhang ◽  
...  

Abstract Traumatic brain injury (TBI) leads to cell and tissue impairment, as well as functional deficits. Stem cells promote structural and functional recovery and thus are considered as a promising therapy for various nerve injuries. Here, we aimed to investigate the role of ectoderm-derived frontal bone mesenchymal stem cells (FbMSCs) in promoting cerebral repair and functional recovery in a murine TBI model. FbMSCs showed fibroblast like morphology and osteogenic differentiation capacity. FbMSCs were CD105, CD29 positive and CD45, CD31 negative. Different from mesoderm-derived MSCs, FbMSCs highly expressed ectoderm-specific transcription factor Tfap2β and growth factor FGF1. FbMSC application significantly ameliorated the behavioral deficits of TBI mice and promoted neural regeneration. Immunofluorescence staining and qRT-PCR data revealed that microglial activation and astrocyte polarization to the A1 phenotype were suppressed by FbMSC application. In addition, FGF1 secreted from FbMSCs enhanced glutamate transportation by astrocytes and alleviated the cytotoxic effect of excessive glutamate on neurons. Therefore, MSCs with characteristics of FbMSCs might be good candidates for TBI therapy.


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