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脊髓损伤后输注同种异体脐带间充质干细胞后大鼠运动功能的早期和持续改善。

Early and sustained improvements in motor function in rats after infusion of allogeneic umbilical cord-derived mesenchymal stem cells following spinal cord injury.

机构信息

Mayo Clinic Neuro-Informatics Laboratory, Mayo Clinic, Rochester, MN, USA.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.

出版信息

Spinal Cord. 2021 Mar;59(3):319-327. doi: 10.1038/s41393-020-00571-8. Epub 2020 Nov 2.

DOI:10.1038/s41393-020-00571-8
PMID:33139846
Abstract

STUDY DESIGN

Animal study.

OBJECTIVES

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have recently been shown to hold great therapeutic potential for spinal cord injury (SCI). However, majority of the studies have been done using human cells transplanted into the rat with immunosuppression; this may not represent the outcomes that occur in humans. Herein, we present the therapeutic effect of using rat UC-MSCs (rUC-MSC) without immunosuppression in a rat model of SCI.

SETTING

Mayo Clinic, Rochester, MN, USA.

METHODS

Twelve female rats were randomly divided into two groups, control, and rUC-MSC group, and then subjected to a T9 moderate contusion SCI. Next, 2 × 10 rUC-MSCs or ringer-lactate solution were injected through the tail vein at 7 days post injury. Rats were assessed for 14 weeks by an open-field Basso, Beattie, and Bresnahan (BBB) motor score as well as postmortem quantification of axonal sparing/regeneration, cavity volume, and glial scar.

RESULTS

Animals treated with rUC-MSCs were found to have early and sustained motor improvement (BBB score of 14.6 ± 1.9 compared to 10.1 ± 1.7 in the control group) at 14 weeks post injury (mean difference: 4.55, 95% CI: 2.04 to 7.06; p value < 0.001). Total cavity volume in the injury epicenter was significantly reduced in the rUC-MSC group; control: 33.0% ± 2.1, rUC-MSC: 25.3% ± 3.8 (mean difference: -7.7% (95% CI: -12.3 to -2.98); p value < 0.05). In addition, spinal cords from rats treated with rUC-MSCs were found to have a significantly greater number of myelinated axons, decreased astrogliosis, and reduced glial scar formation compared to control rats.

CONCLUSIONS

Our study indicates that intravenous injection of allogenic UC-MSCs without immunosuppression exert beneficial effects in subacute SCI and thus could be a useful therapy to improve the functional capacity among patients with SCI.

摘要

研究设计

动物研究。

目的

脐带间充质干细胞(UC-MSCs)最近被证明对脊髓损伤(SCI)具有很大的治疗潜力。然而,大多数研究都是使用移植到免疫抑制大鼠体内的人细胞进行的;这可能无法代表发生在人类身上的结果。在此,我们介绍了在 SCI 大鼠模型中不使用免疫抑制的大鼠 UC-MSCs(rUC-MSC)的治疗效果。

地点

美国明尼苏达州罗切斯特市梅奥诊所。

方法

12 只雌性大鼠随机分为对照组和 rUC-MSC 组,然后接受 T9 中度挫伤 SCI。接着,在损伤后 7 天,通过尾静脉注射 2×10 rUC-MSCs 或林格氏乳酸溶液。通过开放式 Basso、Beattie 和 Bresnahan(BBB)运动评分以及轴突保留/再生、腔体积和神经胶质瘢痕的死后定量评估,在 14 周内对大鼠进行评估。

结果

与对照组(10.1±1.7)相比,接受 rUC-MSCs 治疗的动物在损伤后 14 周时表现出早期和持续的运动改善(BBB 评分 14.6±1.9)(平均差异:4.55,95%置信区间:2.04 至 7.06;p 值<0.001)。rUC-MSC 组损伤中心的总腔体积明显减少;对照组:33.0%±2.1,rUC-MSC:25.3%±3.8(平均差异:-7.7%(95%置信区间:-12.3 至-2.98);p 值<0.05)。此外,与对照组大鼠相比,接受 rUC-MSCs 治疗的大鼠脊髓中的髓鞘化轴突数量明显增加,星形胶质增生减少,神经胶质瘢痕形成减少。

结论

我们的研究表明,静脉注射同种异体 UC-MSCs 而不进行免疫抑制可在亚急性 SCI 中发挥有益作用,因此可能是一种改善 SCI 患者功能能力的有用疗法。

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