人脐带间充质干细胞移植修复兔退变椎间盘的初步研究

A preliminary study of transplantation of human umbilical cord mesenchymal stem cell in a rabbit model of intervertebral disc degeneration

背景:大量研究证实,骨髓间充质干细胞在体外和体内均可向椎间盘样细胞分化,并初步用于治疗椎间盘退变。与骨髓间充质干细胞相比,人脐带间充质干细胞(UCMSCs)具有明显的优势:1成本较低;2来源丰富;3不会给捐献者造成新的创伤和痛苦;4不涉及伦理问题;5可塑性强;6扩增能力强;7无致瘤活性和低免疫原性;8不会随着传代次数增加导致增殖能力和分化能力降低。目的:探索UCMSCs修复椎间盘退变的可能性。方法法:体外培养UCMSCs,髓核抽吸法建立兔椎间盘退变模型,将UCMSCs移植到退变的兔椎间盘中,4、8、12周后行X线、MRI检查,并取材行髓核蛋白多糖检测,检测修复效果。本实验按照椎间盘节段分组,每只兔子的L2/3为退变组,L3/4为PBS注射组,L4/5为UCMSCs移植组,L5/6为空白对照组。应用图像处理软件对X线图像进行分析。采用椎间盘高度指数(DHI)评估椎间盘高度变化。结果:术后4、8、12周,退变组与对照组相比,DHI%值和髓核蛋白多糖含量明显降低,MRI T2WI分级明显升高,且均有统计学差异(P<0.05)。UCMSCs移植组与PBS注射组比,DHI%值和髓核蛋白多糖含量有所升高,MRI T2WI分级有所降低,在术后12周时两组比较具有显著统计学差异(P<0.05)。结论:髓核抽吸法成功建立了兔椎间盘退变模型,移植UCMSCs可以有效修复兔椎间盘的退变。

Background： A large amount of researches confirmed that bone marrow mesenchymal stem cells is able to differentiate into intervertebral disc cells both in vitro and in vivo, and preliminarily used for the treatment of intervertebral disc degeneration.Compared with bone marrow mesenchymal stem cells, human umbilical cord mesenchymal stem cells（UCMSCs） have obvious advantages： low cost, wide sources, not causing new trauma and pain for the donor, not involving ethical issues, stronger plasticity and amplification ability, non-tumorigenic activity and low-immunogenicity, no decrease of proliferation ability or differentiation ability with passage number and body age increasing.Objective： The purpose of the study is to evaluate whether injections of UCMSCs had regenerative effects on intervertebral disc degeneration in a rabbit model.Methods： UCMSCs were cultured in vitro. Four continuous lumbar discs were injured by aspirating nucleus pulposus in rabbits to induce disc degeneration and then the rabbits were treated by injection with UCMSCs or phosphate buffered saline（PBS）. At 4, 8, and 12 weeks after initial injection, rabbits were performed by X- rays and magnetic resonance imaging（MRI）, and ther they were sacrificed and the spine was extracted for detecting proteoglycan content.Results： DHI（disc height index） and proteoglycan content showed significantly lower in the degenerated group as compared with the control group, while the MRI grade showed the opposite change at 4, 8, and 12 weeks after initial injection（P〈0.05）. DHI and proteoglycan content in the UCMSCs-injected group were significantly higher than those in the PBS-injected group at 12 weeks after injection, but the MRI grade showed the opposite change（P〈0.05）.Conclusions： The results of our study indicate that UCMSCs is a promising candidate for the treatment of the degenerative disc disease.