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输注异体培养间充质干细胞治疗创伤性脑损伤小鼠的疗效观察:一项质子磁共振波谱纵向评估。

Therapeutic Prospective of Infused Allogenic Cultured Mesenchymal Stem Cells in Traumatic Brain Injury Mice: A Longitudinal Proton Magnetic Resonance Spectroscopy Assessment.

机构信息

NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Defense Research and Development Organisation, Timarpur, Delhi, India.

Division of Stem Cell and Gene Therapy Research, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Timarpur, Delhi, India.

出版信息

Stem Cells Transl Med. 2017 Jan;6(1):316-329. doi: 10.5966/sctm.2016-0087. Epub 2016 Aug 8.

Abstract

Improved therapeutic assessment of experimental traumatic brain injury (TBI), using mesenchymal stem cells (MSCs), would immensely benefit its therapeutic management. Neurometabolite patterns at injury site, measured with proton magnetic resonance spectroscopy (1H-MRS) after MSCs transplantation, may serve as a bio-indicator of the recovery mechanism. This study used in vivo magnetic resonance imaging and 1H-MRS to evaluate the therapeutic prospects of implanted MSCs at injury site in experimental mice longitudinally up to 21 days. Negative tissue contrast and cytotoxic edema formation were observed in susceptibility-based contrast (T2*) and an apparent diffusion coefficient map, respectively. Lesion site showed decreased N-acetylaspartate, total choline, myo-inositol, total creatine, glutamate-glutamine complex, and taurine neurometabolic concentrations by 1H-MRS investigation. There was a considerable decrease in locomotor activity, depression index, and cognitive index after TBI. It may, therefore, be inferred that MSC transplantation prompted recovery by decreasing negative signals and edema, restoring metabolites to baseline concentrations, and enhancing behavioral activity. Overall findings support the potential of MSC transplantation for the enhancement of endogenous neuroprotective responses, which may provide future clinical applications for translating laboratory research into therapeutic clinical advances. Stem Cells Translational Medicine 2017;6:316-329.

摘要

改善实验性创伤性脑损伤 (TBI) 的治疗评估,使用间充质干细胞 (MSCs),将极大地有益于其治疗管理。在 MSCs 移植后,通过质子磁共振波谱 (1H-MRS) 测量损伤部位的神经代谢物模式,可作为恢复机制的生物指标。本研究使用体内磁共振成像和 1H-MRS 来评估实验小鼠损伤部位植入 MSCs 的治疗前景,最长可达 21 天。在基于敏感性的对比 (T2*) 和表观扩散系数图中,分别观察到负组织对比和细胞毒性水肿形成。通过 1H-MRS 研究发现,损伤部位的 N-乙酰天冬氨酸、总胆碱、肌醇、总肌酸、谷氨酸-谷氨酰胺复合物和牛磺酸神经代谢物浓度降低。TBI 后运动活动、抑郁指数和认知指数显著降低。因此,可以推断 MSC 移植通过减少负信号和水肿、将代谢物恢复到基线浓度以及增强行为活动来促进恢复。总体研究结果支持 MSC 移植增强内源性神经保护反应的潜力,这可能为将实验室研究转化为治疗临床进展提供未来的临床应用。《干细胞转化医学》2017 年;6:316-329。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b830/5442758/c6bca678a474/SCT3-6-316-g001.jpg

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