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.
引用
收藏
页码:420 / 430
页数:11
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