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骨髓间充质干细胞移植治疗帕金森病大鼠模型后多巴胺转运体结合活性的改善:采用 F-18 FP-CIT 进行小动物正电子发射断层扫描研究。

Improved dopamine transporter binding activity after bone marrow mesenchymal stem cell transplantation in a rat model of Parkinson's disease: small animal positron emission tomography study with F-18 FP-CIT.

机构信息

Department of Nuclear Medicine and Molecular Imaging, School of Medicine, Ajou University, Woncheon-dong, Yeongtong-gu, Gyeonggi-do, Suwon, Korea, 443-749.

出版信息

Eur Radiol. 2015 May;25(5):1487-96. doi: 10.1007/s00330-014-3549-3. Epub 2014 Dec 11.

DOI:10.1007/s00330-014-3549-3
PMID:25504429
Abstract

OBJECTIVES

We evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) in a model of Parkinson's disease (PD) using serial F-18 fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) PET.

METHODS

Hemiparkinsonian rats were treated with intravenously injected BMSCs, and animals without stem cell therapy were used as the controls. Serial FP-CIT PET was performed after therapy. The ratio of FP-CIT uptake in the lesion side to uptake in the normal side was measured. The changes in FP-CIT uptake were also analyzed using SPM. Behavioural and histological changes were observed using the rotational test and tyrosine hydroxylase (TH)-reactive cells.

RESULTS

FP-CIT uptake ratio was significantly different in the BMSCs treated group (n = 28) at each time point. In contrast, there was no difference in the ratio in control rats (n = 25) at any time point. SPM analysis also revealed that dopamine transporter binding activity was enhanced in the right basal ganglia area in only the BMSC therapy group. In addition, rats that received BMSC therapy also exhibited significantly improved rotational behaviour and preservation of TH-positive neurons compared to controls.

CONCLUSIONS

The therapeutic effect of intravenously injected BMSCs in a rat model of PD was confirmed by dopamine transporter PET imaging, rotational functional studies, and histopathological evaluation.

KEY POINTS

• Mesenchymal stem cells were intravenously injected to treat the PD rats • Dopamine transporter binding activity was improved after stem cell therapy • Stem cell therapy induced functional recovery and preservation of dopaminergic neurons • The effect of stem cells was confirmed by FP-CIT PET.

摘要

目的

我们使用连续 F-18 氟丙基羰甲基碘苯诺特罗(FP-CIT)正电子发射断层扫描(PET)评估骨髓间充质干细胞(BMSCs)在帕金森病(PD)模型中的作用。

方法

对偏侧帕金森病大鼠进行静脉注射 BMSC 治疗,未接受干细胞治疗的动物作为对照组。治疗后进行连续 FP-CIT PET。测量病变侧与正常侧 FP-CIT 摄取的比值。使用 SPM 分析 FP-CIT 摄取的变化。使用旋转试验和酪氨酸羟化酶(TH)反应性细胞观察行为学和组织学变化。

结果

在每个时间点,BMSC 治疗组(n=28)的 FP-CIT 摄取比值均有显著差异。相比之下,在任何时间点,对照组大鼠(n=25)的比值均无差异。SPM 分析还显示,只有在 BMSC 治疗组中,右侧基底节区域的多巴胺转运体结合活性增强。此外,与对照组相比,接受 BMSC 治疗的大鼠的旋转行为也显著改善,且 TH 阳性神经元保存完好。

结论

通过多巴胺转运体 PET 成像、旋转功能研究和组织病理学评估,证实了静脉注射 BMSC 对 PD 大鼠的治疗效果。

关键点

• 静脉注射间充质干细胞治疗 PD 大鼠

• 干细胞治疗后多巴胺转运体结合活性改善

• 干细胞治疗诱导多巴胺能神经元功能恢复和保存

• FP-CIT PET 证实了干细胞的效果。

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