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应用同种异体脂肪组织来源间充质干细胞条件培养液治疗拉布拉多猎犬双侧肘关节炎的研究。

Study of bilateral elbow joint osteoarthritis treatment using conditioned medium from allogeneic adipose tissue-derived MSCs in Labrador retrievers.

机构信息

Small Animal Clinic, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia.

Associated Tissue Bank, Faculty of Medicine, P. J. Safarik University and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Košice, Slovakia.

出版信息

Res Vet Sci. 2020 Oct;132:513-520. doi: 10.1016/j.rvsc.2020.08.004. Epub 2020 Aug 8.

Abstract

Canine elbow dysplasia is a common cause of forelimb lameness in dogs and can lead to development of osteoarthritis (OA). A potential alternative to pain management is the use of a safe cell-free based therapy through trophic and paracrine factors of mesenchymal stem cells (MSCs). The aim of study was to identify the profile of selected mediators of potential clinical relevance in synovial fluid (SF) samples of dogs with elbow OA and analyse the range of motion (ROM) before and after cell-free MSCs-based treatment. In this study, conditioned medium from allogeneic canine adipose tissue - derived MSC (CM-AD-MSC) was prepared and administered into both elbow joints with OA in six Labrador retriever dogs (n = 6) on day 0 and 14 without creating a control group with a placebo. The SF of the elbow joints was analysed for the presence of several biomolecules (IL-6, IL-10, IL-8, IL-2, IL-12, TNF-αIFN-γ, MMP-3TIMP-1) before and after intraarticular applications of CM-AD-MSC. Kinematic analysis was used to assess the clinical effect of CM-AD-MSC. Analyses of SF and ROM were performed on days 0, 14 and 42. Concentration levels of MMP-3, TIMP-1, IL-6 and TNF-α in SF showed significant differences before and after the treatment (P < .05). There was a significant improvement in ROM between day 0 and 42 (P < .001). No severe adverse events were observed during the study. Results support the potential supportive effect of CM-AD-MSC as a noninvasive therapeutic tool for pain management of OA elbow joints in dogs.

摘要

犬肘关节发育不良是犬前肢跛行的常见原因,并可导致骨关节炎(OA)的发展。替代疼痛管理的一种潜在方法是使用基于无细胞的安全疗法,通过间充质干细胞(MSCs)的营养和旁分泌因子。本研究的目的是确定在患有肘关节炎的犬的滑液(SF)样本中具有潜在临床相关性的选定介质的特征,并分析细胞外 MSC 治疗前后的关节活动度(ROM)。在这项研究中,制备了同种异体犬脂肪组织衍生 MSC(CM-AD-MSC)的条件培养基,并在 6 只拉布拉多猎犬的 OA 双侧肘关节炎关节中在第 0 天和第 14 天进行了给药(n=6),而没有使用安慰剂创建对照组。在关节内应用 CM-AD-MSC 前后,分析了肘关节炎关节 SF 中几种生物分子(IL-6、IL-10、IL-8、IL-2、IL-12、TNF-αIFN-γ、MMP-3TIMP-1)的存在情况。使用运动学分析来评估 CM-AD-MSC 的临床效果。在第 0、14 和 42 天进行了 SF 和 ROM 的分析。SF 中的 MMP-3、TIMP-1、IL-6 和 TNF-α浓度水平在治疗前后显示出显著差异(P<0.05)。ROM 在第 0 天和第 42 天之间有显著改善(P<0.001)。在研究过程中未观察到严重不良事件。结果支持 CM-AD-MSC 作为一种非侵入性治疗工具,具有治疗犬 OA 肘关节炎疼痛的潜在支持作用。

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