Department of Bioengineering, Rice University, Houston, Texas, USA.
Tissue Eng Part A. 2012 Mar;18(5-6):568-75. doi: 10.1089/ten.TEA.2011.0226. Epub 2011 Nov 4.
Immune rejection is a major concern for any allogeneic or xenogeneic graft. For in vivo investigations of cartilage tissue engineering strategies, small animal models such as the leporine model are commonly employed. Many studies report little to no immune rejection upon allogeneic or xenogeneic implantation of native articular and meniscal cartilages. This study investigated whether bovine and leporine articular chondrocytes (ACs) and meniscus cells (MCs) have immunoprivileged characteristics because of their ability to stimulate proliferation of leporine peripheral blood mononuclear cells (PBMCs) in vitro. After 6 days of co-culture, none of the cell types caused a proliferative response in the leporine PBMCs, indicating that these cells may not elicit immune rejection in vivo. Reverse transcriptase polymerase chain reaction analysis for major histocompatibility complex class (MHC) I and II and costimulation factors CD80 and CD86 revealed that all cell types produced messenger RNA for MHC I and II, but only some were CD80 or CD86 positive, and none were positive for both costimulation factors. Flow cytometry found that bovine MCs and ACs displayed MHC II (MCs: 32.5%, ACs: 14.4%), whereas only leporine ACs were MHC II positive (7.5%). Although present in isolated cells, MHC I and II were not observed in intact bovine or leporine hyaline cartilage or meniscus tissues. Despite some presence of MHC II and costimulation factors, none of the cell types studied were able to cause PBMC proliferation. These findings indicate that bovine and leporine MCs and ACs share a similar immunoprivileged profile, bolstering their use as allogeneic and xenogeneic cell sources for engineered cartilage.
免疫排斥是同种异体或异种移植物的主要关注点。在软骨组织工程策略的体内研究中,通常使用小型动物模型,如兔模型。许多研究报告称,同种异体或异种植入关节和半月板的天然软骨几乎没有免疫排斥。本研究探讨了牛和兔关节软骨细胞(AC)和半月板细胞(MC)是否具有免疫特权特性,因为它们能够刺激兔外周血单核细胞(PBMC)在体外增殖。在共培养 6 天后,没有一种细胞类型引起兔 PBMC 的增殖反应,这表明这些细胞在体内可能不会引起免疫排斥。主要组织相容性复合体(MHC)I 和 II 类和共刺激因子 CD80 和 CD86 的逆转录聚合酶链反应分析表明,所有细胞类型均产生 MHC I 和 II 的信使 RNA,但只有一些细胞为 CD80 或 CD86 阳性,没有一种细胞同时为两种共刺激因子阳性。流式细胞术发现牛 MC 和 AC 均显示 MHC II(MC:32.5%,AC:14.4%),而只有兔 AC 呈 MHC II 阳性(7.5%)。尽管在分离细胞中存在,但完整的牛或兔透明软骨或半月板组织中未观察到 MHC I 和 II。尽管存在 MHC II 和共刺激因子,但研究的细胞类型均无法引起 PBMC 增殖。这些发现表明,牛和兔的 MC 和 AC 具有相似的免疫特权特征,支持它们作为工程化软骨的同种异体和异种细胞来源。