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Chondroitin Sulfate Glycosaminoglycan Matrices Promote Neural Stem Cell Maintenance and Neuroprotection Post-Traumatic Brain Injury
被引:47
|作者:
Betancur, Martha I.
[1
]
Mason, Hannah D.
[1
]
Alvarado-Velez, Melissa
[3
]
Holmes, Phillip V.
[2
]
Bellamkonda, Ravi V.
[3
]
Karumbaiah, Lohitash
[1
]
机构:
[1] Univ Georgia, Regenerat Biosci Ctr, 425 River Rd,ADS Complex, Athens, GA 30602 USA
[2] Univ Georgia, Dept Psychol, 125 Baldwin St, Athens, GA 30602 USA
[3] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, 313 Ferst Dr, Atlanta, GA 30332 USA
来源:
基金:
美国国家卫生研究院;
关键词:
traumatic brain injury;
biomaterials;
neuroprotection;
chondroitin sulfate glycosaminoglycan;
neural stem cells;
hydrogels;
GROWTH-FACTORS;
STEM/PROGENITOR CELLS;
GLIAL SCAR;
PROTEOGLYCAN;
PROLIFERATION;
NEUROGENESIS;
BINDING;
DIFFERENTIATION;
REGENERATION;
REGIONS;
D O I:
10.1021/acsbiomaterials.6b00805
中图分类号:
TB3 [工程材料学];
R318.08 [生物材料学];
学科分类号:
0805 ;
080501 ;
080502 ;
摘要:
There are currently no effective treatments for moderate-to-severe traumatic brain injuries (TBIs). The paracrine functions of undifferentiated neural stem cells (NSCs) are believed to play a significant role in stimulating the repair and regeneration of injured brain tissue. We therefore hypothesized that fibroblast growth factor (FGF2) enriching chondroitin sulfate glycosaminoglycan (CS-GAG) matrices can maintain the undifferentiated state of neural stem cells (NSCs) and facilitate brain tissue repair subacutely post-TBI. Rats subjected to a controlled cortical impactor (CCI) induced TBI were intraparenchymally injected with CS-GAG matrices alone or with CS-GAG matrices containing PKH26GL labeled allogeneic NSCs. Nissl staining of brain tissue 4 weeks post-TBI demonstrated the significantly enhanced (p < 0.05) tissue protection in CS-GAG treated animals when compared to TBI only control, and NSC only treated animals. CS-GAG-NSC treated animals demonstrated significantly enhanced (p < 0.05) FGF2 retention, and maintenance of PKH26GL labeled NSCs as indicated by enhanced Soxl+ and Ki67+ cell presence over other differentiated cell types. Lastly, all treatment groups and sham controls exhibited a significantly (p < 0.05) attenuated GFAP+ reactive astrocyte presence in the lesion site when compared to TBI only controls.
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页码:420 / 430
页数:11
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