细胞因子表达谱在人脐带Wharton胶间质干细胞诱导分化成软骨细胞的变化

目的]观察从人脐带Wharton' s胶中分离的间质干细胞(WMSC)诱导分化成软骨细胞时表达细胞因子及生长因子的异同,从而为WMSC诱导的软骨细胞用于组织工程的构建以及其在临床的应用打下基础.方法]从人正常足月分娩的脐带中分离间质干细胞,在体外以条件培基诱导分化成软骨细胞,免疫组化法鉴定其特性,应用细胞因子蛋白芯片方法检测WMSC及其诱导分化的软骨细胞所表达细胞因子及生长因子,并取成年人正常关节软骨为对照.结果]78种细胞因子和生长因子在WMSC及其诱导分化的软骨细胞均有表达,两者表达谱相同,而表达量则多少有不同.诱导分化后表达量增多的因子为:MIP-3α,ENA-78,VEGF,PDGF-BB,SCF,FGF-7,GCP-2及SDF-1.减少的因子为MIP-1βHGF,NT-4,IL-10及MIP-δ.其共同表达的具免疫抑制作用的因子对降低异体移植时的免疫排斥可能有一定作用,其共同表达的金属蛋白酶抑制因子对其移植于体内时可具有保护作用.而共同表达的肿瘤生长抑制因子则可减少对干细胞移植后瘤变的担心.结论]从人脐带wharton' s胶中分离的间质干细胞(WMSC)诱导分化成软骨细胞时表达细胞因子及生长因子谱相同,是一种理想的可替代自身软骨细胞的新型种子细胞,用于构建工程软骨组织.

Changes of cytokine profile during the differentiation from human umbilicord Wharton's jelly mesenchymal stem cells to cartilage cells

Objective] To study cytokine and growth factor expression patterns of chondrocytes differentiated from mesen-chymal cells isolated from human umbilical cord Wharton's jelly and of normal adult articular chondrocytes.Methods] Fresh umbilical cord were collected from healthy donor full - term births. Mesenchymal stem cells were isolated from Wharton's jelly of two human unbilical cords and cultured in conditional medium to differentiate to cartilage cells. Immunochemical staining method was used to identify the cartilage cell phenotype. Normal adult articular cartilage cells were isolated from one donor. Cytokine antibody - array technology (Clontech) was used to analyze cytokines and growth factors.Results] The cytokine and growth factor profiles of chondrocytes differentiated from WMSC (Wharton jelly MSC) and normal cartilage cells were similar, but the expression level was somewhat different The maximum expression in chondrocyte were: MIP-3α, ENA -78, VEGF, PDGF -BB, SCF, FGF-7, GCP -2 and SDF-1. The decreased factors were : MIP-Iβ, HGF, NT-4, IL-10 and MIP-δ. A range of soluble immune tolerant factors IL - 10, TGF, VEGF and HGF were expressed in significant amount, thus creating a local immunosuppressive environment This result suggests that those factors may contribute to the ability of WMSC to avoid al-lorejection.WMSC and derived cartilage cell can produce oncostatin M and LIGHT, and high level of TIMP-1 and TIMP-2, which may help for prevent malignant change and enzyme digestion in vivo during transplantation. Conclusion ] These findings should encourage the use of mesenchymal stem cells from Wharton ' s jelly of human umbilical cord as a potential new seed cells in cartilage tissue engineering.