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马源性诱导性软骨细胞间充质干细胞治疗骨关节炎:一项随机、双盲、安慰剂对照的概念验证研究。

The use of equine chondrogenic-induced mesenchymal stem cells as a treatment for osteoarthritis: A randomised, double-blinded, placebo-controlled proof-of-concept study.

机构信息

Global Stem Cell Technology NV, Anacura Group, Evergem, Belgium.

Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

出版信息

Equine Vet J. 2019 Nov;51(6):787-794. doi: 10.1111/evj.13089. Epub 2019 Apr 13.

Abstract

BACKGROUND

There is a need to improve therapies for osteoarthritis in horses.

OBJECTIVES

To assess the efficacy of equine allogeneic chondrogenic-induced mesenchymal stem cells combined with equine allogeneic plasma as a novel therapy for osteoarthritis in horses.

STUDY DESIGN

Randomised, double-blinded, placebo-controlled experiment.

METHODS

In 12 healthy horses, osteoarthritis was induced in the metacarpophalangeal joint using an osteochondral fragment-groove model. Five weeks after surgery, horses were randomly assigned to either an intra-articular injection with chondrogenic-induced mesenchymal stem cells + equine allogeneic plasma (= intervention) or with 0.9% saline solution (= control). From surgery until the study end, horses underwent a weekly joint and lameness assessment. Synovial fluid was collected for cytology and biomarker analysis before surgery and at Weeks 5, 5 + 1d, 7, 9 and 11. At Week 11, horses were subjected to euthanasia, and the metacarpophalangeal joints were evaluated macroscopically and histologically.

RESULTS

No serious adverse events or suspected adverse drug reactions occurred during the study. A significant improvement in visual and objective lameness was seen with the intervention compared with the control. Synovial fluid displayed a significantly higher viscosity and a significantly lower glycosaminoglycan concentration in the intervention group. Other biomarkers or cytology parameters were not significantly different between the treatment groups. Significantly less wear lines and synovial hyperaemia were present in the intervention group. The amount of cartilage oligomeric matrix protein, collagen type II and glycosaminoglycans were significantly higher in the articular cartilage of the intervention group.

MAIN LIMITATIONS

This study assessed the short-term effect of the intervention on a limited number of horses, using an osteoarthritis model. This study also included multiple statistical tests, increasing the risk of type 1 error.

CONCLUSIONS

Equine allogeneic chondrogenic-induced mesenchymal stem cells combined with equine allogeneic plasma may be a promising treatment for osteoarthritis in horses. The Summary is available in Spanish - see Supporting Information.

摘要

背景

需要改进马的骨关节炎治疗方法。

目的

评估马同源软骨诱导间充质干细胞与马同源血浆联合作为马骨关节炎新型治疗方法的疗效。

研究设计

随机、双盲、安慰剂对照实验。

方法

在 12 匹健康马中,使用骨软骨碎片沟模型诱导掌指关节骨关节炎。手术后 5 周,马被随机分为关节内注射软骨诱导间充质干细胞+马同源血浆(=干预组)或 0.9%生理盐水溶液(=对照组)。从手术到研究结束,马每周进行关节和跛行评估。在手术前和第 5、5+1、7、9 和 11 周采集滑液进行细胞学和生物标志物分析。第 11 周,马被安乐死,掌指关节进行宏观和组织学评估。

结果

研究过程中未发生严重不良事件或疑似药物不良反应。与对照组相比,干预组的视觉和客观跛行明显改善。与对照组相比,干预组滑液的粘度显著升高,糖胺聚糖浓度显著降低。两组间其他生物标志物或细胞学参数无显著差异。干预组的磨损线和滑膜充血明显减少。干预组关节软骨中的软骨寡聚基质蛋白、Ⅱ型胶原和糖胺聚糖含量明显升高。

主要局限性

本研究在有限数量的马中评估了该干预措施的短期效果,使用骨关节炎模型。本研究还包括多个统计检验,增加了 I 型错误的风险。

结论

马同源软骨诱导间充质干细胞与马同源血浆联合可能是马骨关节炎有前途的治疗方法。摘要提供西班牙语版本-见支持信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d8/6850029/048ce47dc96b/EVJ-51-787-g001.jpg

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