Co-overexpression of OPN, IGF-1 and CNTF augment the therapeutic effect of DPSC on spinal cord injury

OPN、IGF-1 和 CNTF 的共同过表达增强了 DPSC 对脊髓损伤的治疗效果

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作者:Ning Tao, Xiwen Dong, Chao Liu, Lin Lv, Fanqi Hu, Huan Zhang, Xue Li, Panpan Geng, Han Duan, Chu-Tse Wu, Hua Wang

Aims

Spinal cord injury (SCI) is one of the most complex and destructive diseases of the nervous system, which can lead to permanent loss of tactile perception. But existing treatment

Conclusions

DPSC-OIC could be a novel effective method for treating SCI.

Methods

Adenovirus carrying osteopontin (OPN), Insulin-like growth factor 1 (IGF-1) and cailiary-derived neurotrophic factor (CNTF) (Ad-OIC) was constructed. After modified with Ad-OIC, supernatant of DPSC were co-cultured with HT-22 cells and the effect of DPSC-OIC on the HT-22 cells were evaluated via Cell Counting Kit-8 (CCK-8) assay, Real-Time polymerase chain reaction (PCR) analysis, laser confocal microscopy and fluorescence activating cell sorter (FACS). DPSC-OIC were injected in the lesion area of injured spinal cord and the survival time of transplanted cells were measured by bioluminescence imaging system. The recovery of the injured spinal cord was evaluated by behavioral score, radiological evaluation and immunopathological analysis.

Results

DPSC-OIC could enhance the proliferation and axon growth of HT-22 cells, and protect HT-22 cells from H2O2 induced apoptosis. The transplanted DPSC-Null or DPSC-OIC could survive for more than two weeks in local injection site. DPSC-OIC treatment could increase Basso-Mouse Scale (BMS) scores, improve Magnetic Resonance Imaging (MRI) manifestation and promote bladder function recovery. Less apoptotic neurons and more proliferative cells were found in the lesion area of DPSC-OIC treated spinal cord. Nestin+ cells and neural stem cell marker (Sox2) were both up-regulated after DPSC-OIC treatment. Additionally, inhibitory extracellular matrix proteoglycan Neural/Glial Antigen 2 (NG2) was down-regulated and axon growth promotive factor fibronectin was up-regulated after both DPSC-Null (DPSCs infected with Ad-Null) and DPSC-OIC treatments. Conclusions: DPSC-OIC could be a novel effective method for treating SCI.

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