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[间充质干细胞移植对大鼠脑卒中后大脑形态学变化动态的影响]

[Mesenchymal stem cells transplantation influences upon dynamics of morphological changes in rat brain after stroke].

作者信息

Zin'kova N N, Gilerovich E G, Sokolova I B, Shvedova E V, Bilibina A A, Krugliakov P V, Polyntsev D G

出版信息

Tsitologiia. 2007;49(11):923-32.

Abstract

Study of dynamic morphological changes if the brain after ischemic stroke is an important phase of pre-clinical trial of mesenchymal stem cell (MSC) therapy for this widespread disease. Experoments were carried out in inbred Wistar-Kyoto rats. MSCs were isolated, expanded in culture and labeled with vital fluorescent dye PKH26. Animals were subjected to middle cerebral artery occlusion (MCAO) followed by injection of 5 x 10(6) rat MSCs into the tail vein on the day of MCAO. Control group of animals received PBS injection (negative control). Animals were sacrificed in 1, 2, 3 and 5 days and in 1, 2, 4 and 6 weeks after operation. MSCs were revealed in the brain on the third day transplantation. They distributed around brain vessels in both the ipsilateral and contralateral hemispheres. This pattern of distribution remained unchanged during 6 weeks of observation. It was demonstrated that inflammation process and scar formation in the experimental group progressed 25-30 % faster than in the control group. MSC transplantation stimulated endogenous stem cell proliferation on the subependimal zone of lateral ventricles (subventrecular zone). What is more, MSC injection showed neuroprotective effect: almost all penumbra neurons in animals treated with cell therapy retained their normal structure, whereas in animals of control group penumbra neurons died or had signs of serious damage.

摘要

研究缺血性中风后大脑的动态形态变化是间充质干细胞(MSC)治疗这种常见疾病临床前试验的重要阶段。实验在近交系Wistar-Kyoto大鼠中进行。分离出间充质干细胞,在培养中扩增并用活性荧光染料PKH26标记。动物接受大脑中动脉闭塞(MCAO),然后在MCAO当天通过尾静脉注射5×10⁶个大鼠间充质干细胞。动物对照组接受PBS注射(阴性对照)。在术后1天、2天、3天和5天以及1周、2周、4周和6周处死动物。移植后第三天在大脑中发现了间充质干细胞。它们分布在同侧和对侧半球的脑血管周围。在6周的观察期内,这种分布模式保持不变。结果表明,实验组的炎症过程和瘢痕形成比对照组快25%-30%。间充质干细胞移植刺激了侧脑室室管膜下区(室管膜下区)内源性干细胞的增殖。此外,间充质干细胞注射显示出神经保护作用:接受细胞治疗的动物中几乎所有半暗带神经元都保持了正常结构,而对照组动物的半暗带神经元死亡或有严重损伤的迹象。

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