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使用间充质干细胞治疗马软骨损伤的概念与挑战

Concepts and challenges in the use of mesenchymal stem cells as a treatment for cartilage damage in the horse.

作者信息

Zayed Mohammed, Adair Steve, Ursini Tena, Schumacher James, Misk Nabil, Dhar Madhu

机构信息

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.

Department of Animal Surgery, College of Veterinary Medicine, Assuit University, 71526 Assuit, Egypt.

出版信息

Res Vet Sci. 2018 Jun;118:317-323. doi: 10.1016/j.rvsc.2018.03.011. Epub 2018 Mar 20.

Abstract

Osteoarthritis (OA), the most common form of joint disease affecting humans and horses, is characterized by the advance and decline of cartilage and loss of function of the affected joint. The progression of OA is steadily accompanied with biochemical events, which interfere with the cytokines and proteolytic enzymes responsible for progress of the disease. Recently, regenerative therapies have been used with an assumption that mesenchymal stem cells (MSCs) possess the potential to prevent the advancement of cartilage damage and potentially regenerate the injured tissue with an ultimate goal of preventing OA. We believe that despite various challenges, the use of allogenic versus autologous MSCs in cartilage regeneration, is a major issue which can directly or indirectly affect the other factors including, the timing of implantation, dose or cell numbers for implantation, and the source of MSCs. Current knowledge reporting some of these challenges that the clinicians might face in the treatment of cartilage damage in horses are presented. In this regard we conducted two independent studies. In the first study we compared donor matched bone marrow and synovial fluid - derived equine MSCs in vitro, and showed that the SFMSCs were similar to the BMMSCs in their proliferation, expression of CD29, CD44 and CD90, but, exhibited a significantly different chondrogenesis. Additionally, 3.2-21% of all SFMSCs were positive for MHC II, whereas, BMMSCs were negative. In the second study we observed that injection of both the autologous and allogenic SFMSCs into the tarsocrural joint resulted in elevated levels of total protein and total nucleated cell counts. Further experiments to evaluate the in vivo acute or chronic response to allogenic or autologous MSCs are imperative.

摘要

骨关节炎(OA)是影响人类和马匹的最常见的关节疾病形式,其特征是软骨的退变和受损关节功能的丧失。OA的进展始终伴随着生化事件,这些生化事件会干扰负责疾病进展的细胞因子和蛋白水解酶。最近,人们使用再生疗法,假定间充质干细胞(MSCs)具有预防软骨损伤进展的潜力,并有可能使受损组织再生,最终目标是预防OA。我们认为,尽管存在各种挑战,但在软骨再生中使用同种异体与自体MSCs是一个重大问题,它可以直接或间接影响其他因素,包括植入时间、植入剂量或细胞数量以及MSCs的来源。本文介绍了目前关于临床医生在治疗马匹软骨损伤时可能面临的一些挑战的知识。在这方面,我们进行了两项独立研究。在第一项研究中,我们在体外比较了供体匹配的骨髓来源和滑液来源的马MSCs,结果表明,滑液间充质干细胞(SFMSCs)在增殖、CD29、CD44和CD90的表达方面与骨髓间充质干细胞(BMMSCs)相似,但软骨形成明显不同。此外,所有SFMSCs中有3.2%-21%的细胞MHC II呈阳性,而BMMSCs为阴性。在第二项研究中,我们观察到将自体和同种异体SFMSCs注射到跗关节中会导致总蛋白水平和总核细胞计数升高。进一步评估同种异体或自体MSCs体内急性或慢性反应的实验势在必行。

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