关节内注射自体和同种异体胎盘来源的马间充质干细胞后的临床病理观察。
Clinicopathologic findings following intra-articular injection of autologous and allogeneic placentally derived equine mesenchymal stem cells in horses.
机构信息
Department of Pathology, Microbiology and Immunology, University of California, Davis, California 95616, USA.
出版信息
Cytotherapy. 2011 Apr;13(4):419-30. doi: 10.3109/14653249.2010.536213. Epub 2010 Nov 25.
BACKGROUND AIMS
The development of an allogeneic mesenchymal stem cell (MSC) product to treat equine disorders would be useful; however, there are limited in vivo safety data for horses. We hypothesized that the injection of self (autologous) and non-self (related allogeneic or allogeneic) MSC would not elicit significant alterations in physical examination, gait or synovial fluid parameters when injected into the joints of healthy horses.
METHODS
Sixteen healthy horses were used in this study. Group 1 consisted of foals (n = 6), group 2 consisted of their dams (n = 5) and group 3 consisted of half-siblings (n = 5) to group 1 foals. Prior to injection, MSC were phenotyped. Placentally derived MSC were injected into contralateral joints and MSC diluent was injected into a separate joint (control). An examination, including lameness evaluation and synovial fluid analysis, was performed at 0, 24, 48 and 72 h post-injection.
RESULTS
MSC were major histocompatibility complex (MHC) I positive, MHC II negative and CD86 negative. Injection of allogeneic MSC did not elicit a systemic response. Local responses such as joint swelling or lameness were minimal and variable. Intra-articular MSC injection elicited marked inflammation within the synovial fluid (as measured by nucleated cell count, neutrophil number and total protein concentration). However, there were no significant differences between the degree and type of inflammation elicited by self and non-self-MSC.
CONCLUSIONS
The healthy equine joint responds similarly to a single intra-articular injection of autologous and allogeneic MSC. This pre-clinical safety study is an important first step in the development of equine allogeneic stem cell therapies.
背景目的
开发用于治疗马科动物疾病的同种异体间充质干细胞(MSC)产品将是有益的;然而,马科动物的体内安全性数据有限。我们假设,当将自体(自体)和非自体(相关同种异体或同种异体)MSC 注射到健康马的关节中时,不会引起体检、步态或滑液参数的显著变化。
方法
本研究使用了 16 匹健康马。第 1 组由小马(n = 6)组成,第 2 组由它们的母马(n = 5)组成,第 3 组由与第 1 组小马的半同胞(n = 5)组成。注射前,对 MSC 进行了表型鉴定。胎盘来源的 MSC 被注射到对侧关节,MSC 稀释液被注射到另一个关节(对照)。在注射后 0、24、48 和 72 小时进行检查,包括跛行评估和滑液分析。
结果
MSC 主要组织相容性复合体(MHC)I 阳性,MHC II 阴性,CD86 阴性。同种异体 MSC 注射不会引起全身反应。局部反应如关节肿胀或跛行轻微且多变。关节内 MSC 注射会引起滑液内明显炎症(通过有核细胞计数、中性粒细胞数量和总蛋白浓度来衡量)。然而,自体和非自体-MSC 引起的炎症程度和类型没有显著差异。
结论
健康马关节对单次关节内注射自体和同种异体 MSC 的反应相似。这项临床前安全性研究是开发马科动物同种异体干细胞疗法的重要第一步。