Zayed Mohammed, Newby Steven, Misk Nabil, Donnell Robert, Dhar Madhu
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Comparative and Experimental Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Stem Cells Int. 2018 Jun 6;2018:1073705. doi: 10.1155/2018/1073705. eCollection 2018.
Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs' treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.
马被广泛用作软骨修复研究的大型动物临床前模型,因此,人们对在研究和临床应用中使用马滑膜来源的间充质干细胞(SFMSCs)很感兴趣。由于我们之前曾报道,与骨髓来源的间充质干细胞(BMMSCs)类似,SFMSCs在干细胞特性方面也可能存在供体间差异;本研究作为一项概念验证研究进行,旨在比较马BMMSCs和SFMSCs在关节软骨修复中的体内潜力。这两种来源的间充质干细胞均从同一匹马的供体中分离得到。体外分析证实,第14天时SFMSCs中COMP表达显著增加。然后将细胞封装在中性琼脂糖支架构建物中,并植入大鼠股骨滑车沟直径为2毫米的全层关节软骨缺损处。对间充质干细胞进行荧光标记,治疗一周后,评估膝关节损伤部位是否存在间充质干细胞,12周时进行宏观、组织学评估,然后通过免疫荧光评估缺损的愈合情况。宏观和组织学评估显示,间充质干细胞治疗的膝关节软骨愈合情况优于对照组。有趣的是,经SFMSC治疗的膝关节Col II表达显著更高,表明愈合缺损处存在透明软骨。数据表明,马SFMSCs可能是治疗骨软骨缺损的可行选择;然而,在应用前需要对其干细胞特性进行预先测试。