Igarashi Akira, Segoshi Kazumi, Sakai Yuhiro, Pan Haiou, Kanawa Masami, Higashi Yukihito, Sugiyama Masaru, Nakamura Kozo, Kurihara Hidemi, Yamaguchi Satoru, Tsuji Koichiro, Kawamoto Takeshi, Kato Yukio
Department of Dental and Medical Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Tissue Eng. 2007 Oct;13(10):2405-17. doi: 10.1089/ten.2006.0340.
Bone marrow stromal cells (BMSCs) are valuable in tissue engineering and cell therapy, but the quality of the cells is critical for the efficacy of therapy. To test the quality and identity of transplantable cells, we identified the molecular markers that were expressed at higher levels in BMSCs than in fibroblasts. Using numerous BMSC lines from tibia, femur, ilium, and jaw, together with skin and gum fibroblasts, we compared the gene expression profiles of these cells using DNA microarrays and low-density array cards. The differentiation potential of tibia and femur BMSCs was similar to that of iliac BMSCs, and different from jaw BMSCs, but all BMSC lines had many common markers that were expressed at much higher levels in BMSCs than in fibroblasts; several BMSC markers showed discrete expression patterns between jaw and other BMSCs. The common markers are probably useful in routine tests, but their efficacy may depend upon the passage number or donor age. In our study the passage number markedly altered the expression levels of several markers, while donor age had little effect on them. Considering the effects of in vivo location of BMSCs and passage, magnitude of increase in expression levels, and interindividual differences, we identified several reliable markers -- LIF, IGF1, PRG1, MGP, BMP4, CTGF, KCTD12, IGFBP7, TRIB2, and DYNC1I1 -- among many candidates. This marker set may be useful in a routine test for BMSCs in tissue engineering and cell therapy.
骨髓基质细胞（BMSCs）在组织工程和细胞治疗中具有重要价值，但细胞质量对治疗效果至关重要。为了测试可移植细胞的质量和特性，我们鉴定了在BMSCs中比在成纤维细胞中表达水平更高的分子标志物。我们使用来自胫骨、股骨、髂骨和颌骨的众多BMSC系，以及皮肤和牙龈成纤维细胞，通过DNA微阵列和低密度阵列芯片比较了这些细胞的基因表达谱。胫骨和股骨BMSCs的分化潜能与髂骨BMSCs相似，与颌骨BMSCs不同，但所有BMSC系都有许多共同的标志物，这些标志物在BMSCs中的表达水平远高于成纤维细胞；几种BMSC标志物在颌骨和其他BMSCs之间表现出不同的表达模式。这些共同的标志物可能在常规检测中有用，但其效果可能取决于传代次数或供体年龄。在我们的研究中，传代次数显著改变了几种标志物的表达水平，而供体年龄对其影响不大。考虑到BMSCs的体内位置、传代、表达水平增加的幅度以及个体差异的影响，我们在众多候选标志物中鉴定出了几种可靠的标志物——白血病抑制因子（LIF）、胰岛素样生长因子1（IGF1）、脯氨酸丰富糖蛋白1（PRG1）、基质Gla蛋白（MGP）、骨形态发生蛋白4（BMP4）、结缔组织生长因子（CTGF）、钾通道四聚体化结构域蛋白12（KCTD12）、胰岛素样生长因子结合蛋白7（IGFBP7）、TRIB2和动力蛋白1中间链1（DYNC1I1）。这个标志物组合可能在组织工程和细胞治疗中对BMSCs的常规检测中有用。
