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骨髓间充质基质细胞移植治疗脊髓损伤大鼠模型的功能恢复。

Functional recovery after transplantation of bone marrow-derived human mesenchymal stromal cells in a rat model of spinal cord injury.

机构信息

Stempeutics Research Pvt Ltd, Manipal Hospital, Bangalore, India.

出版信息

Cytotherapy. 2010 Oct;12(6):792-806. doi: 10.3109/14653249.2010.487899.

Abstract

BACKGROUND AIMS

Spinal cord injury (SCI) is a medically untreatable condition for which stem cells have created hope. Pre-clinical and clinical studies have established that these cells are safe for transplantation. The dose dependency, survivability, route of administration, cell migration to injury site and effect on sensory and motor behavior in an SCI-induced paraplegic model were studied.

METHODS

A spinal cord contusion injury model was established in rats. Bone marrow (BM) mesenchymal stromal cells (MSC) were tagged to facilitate tracing in vivo. Two different doses (2 and 5 million cells/kg body weight) and two different routes of infusion (site of injury and lumbar puncture) were tested during and after the spinal shock period. The animals were tested post-transplantation for locomotor capacity, motor control, sensory reflex, posture and body position. Stem cell migration was observed 1 month post-transplantation in spinal cord sections.

RESULTS

The overall results demonstrated that transplantation of BM MSC significantly improved the locomotor and sensory behavior score in the experimental group compared with the sham control group, and these results were dose dependent. All the infused stem cells could be visualized at the site of injury and none was visualized at the injected site. This indicated that the cells had survived in vivo, were probably chemoattracted and had migrated to the lesion site.

CONCLUSIONS

MSC transplanted with a lumbar puncture method migrate to the site of injury and are the most suitable for SCI healing. These cells demonstrate a dose-dependent effect and promote functional recovery when injected during or after the spinal shock period.

摘要

背景目的

脊髓损伤(SCI)是一种医学上无法治疗的疾病,而干细胞为此带来了希望。临床前和临床研究已经证实这些细胞用于移植是安全的。本研究旨在探讨这些细胞在 SCI 诱导的截瘫模型中的剂量依赖性、存活率、给药途径、向损伤部位迁移的能力以及对感觉和运动行为的影响。

方法

建立大鼠脊髓挫伤损伤模型。骨髓(BM)间充质基质细胞(MSC)被标记以方便体内示踪。在脊髓休克期内和之后,测试了两种不同剂量(200 万和 500 万细胞/公斤体重)和两种不同的输注途径(损伤部位和腰椎穿刺)。在移植后,通过运动能力、运动控制、感觉反射、姿势和体位对动物进行测试。在移植后 1 个月观察脊髓切片中干细胞的迁移情况。

结果

总体结果表明,与假手术对照组相比,BM MSC 移植显著改善了实验组的运动和感觉行为评分,且这些结果具有剂量依赖性。所有输注的干细胞都可以在损伤部位观察到,而在注射部位则没有观察到。这表明细胞在体内存活下来,可能受到趋化作用的影响,并迁移到损伤部位。

结论

通过腰椎穿刺方法移植的 MSC 可迁移到损伤部位,最适合 SCI 治疗。这些细胞具有剂量依赖性效应,在脊髓休克期内或之后注射时可促进功能恢复。

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