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大鼠完全性脊髓横断后的植入、神经胶质转分化及行为恢复

Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.

作者信息

Luzzi Sabino, Crovace Alberto Maria, Lacitignola Luca, Valentini Valerio, Francioso Edda, Rossi Giacomo, Invernici Gloria, Galzio Renato Juan, Crovace Antonio

机构信息

Department of Emergency and Organ Transplantation, University of Bari "Aldo Moro", Bari, Italy.

Department of Neurosurgery, San Salvatore City Hospital, L'Aquila, Italy.

出版信息

Surg Neurol Int. 2018 Jan 25;9:19. doi: 10.4103/sni.sni_369_17. eCollection 2018.

Abstract

BACKGROUND

Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration.

METHODS

Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso-Beattie-Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence.

RESULTS

Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions ( <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites.

CONCLUSIONS

Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery.

摘要

背景

异种间充质干细胞(MSCs)移植治疗脊髓损伤(SCI)的有效性和安全性的证据理论上可能会拓宽神经再生可能的移植物范围。

方法

20只大鼠接受完全脊髓横断术。将经逆转录病毒转染红色荧光蛋白且未预先诱导神经胶质分化的绵羊骨髓间充质干细胞应用于10只研究大鼠(MSCG组)。在10只对照大鼠(FGG组)中注射纤维蛋白胶。所有大鼠每周进行评估,并使用Basso-Beattie-Bresnahan(BBB)运动评分量表评分,为期10周,然后对收集的数据进行统计分析。随后取出脊髓,进行光学显微镜、免疫组织化学和免疫荧光分析。

结果

绵羊间充质干细胞培养显示巢蛋白呈阳性。MSCG组运动功能有显著且持久的恢复(P<.001)。在MSCG组的损伤部位发现红色荧光。在相同部位还发现巢蛋白、微管蛋白βIII、NG2胶质细胞、神经元特异性烯醇化酶、波形蛋白和200 kD神经丝呈阳性。

结论

异种绵羊骨髓间充质干细胞被证明能够植入受损大鼠脊髓。向神经胶质表型的转分化能够支持部分功能恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9982/5806420/585f8584fba3/SNI-9-19-g004.jpg

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