Department of Orthopaedic Surgery, University of Connecticut Health Center, 400 Farmington Avenue, Farmington, CT, 06030, USA,
Stem Cell Rev Rep. 2014 Dec;10(6):820-9. doi: 10.1007/s12015-014-9538-8.
The propensity of induced pluripotent stem (iPS) cells to differentiate into specific lineages may be influenced by a number of factors, including the selection of the somatic cell type used for reprogramming. Herein we report the generation of new iPS cells, which we derived from human articular chondrocytes and from cord blood mononucleocytes via lentiviral-mediated delivery of Oct4, Klf4, Sox2, and cMyc. Molecular, cytochemical, and cytogenic analyses confirmed the acquisition of hallmark features of pluripotency, as well as the retention of normal karyotypes following reprogramming of both the human articular chondrocytes (AC) and the cord blood (CB) cells. In vitro and in vivo functional analyses formally established the pluripotent differentiation capacity of all cell lines. Chondrogenic differentiation assays comparing iPS cells derived from AC, CB, and a well established dermal fibroblast cell line (HDFa-Yk26) identified enhanced proteoglycan-rich matrix formation and cartilage-associated gene expression from AC-derived iPS cells. These findings suggest that the tissue of origin may impact the fate potential of iPS cells for differentiating into specialized cell types, such as chondrocytes. Thus, we generated new cellular tools for the identification of inherent features driving high chondrogenic potential of reprogrammed cells.
诱导多能干细胞（iPS）分化为特定谱系的倾向可能受到多种因素的影响，包括用于重编程的体细胞核型的选择。在此，我们报告了通过慢病毒介导的 Oct4、Klf4、Sox2 和 cMyc 的传递，从人关节软骨细胞和脐带血单核细胞中产生的新型 iPS 细胞。分子、细胞化学和细胞遗传学分析证实了多能性标志性特征的获得，以及在重编程人关节软骨细胞（AC）和脐带血（CB）细胞后正常核型的保留。体外和体内功能分析正式确立了所有细胞系的多能分化能力。比较源自 AC、CB 和已建立的真皮成纤维细胞系（HDFa-Yk26）的 iPS 细胞的软骨分化分析鉴定出源自 AC 的 iPS 细胞中富含蛋白聚糖的基质形成和与软骨相关的基因表达增强。这些发现表明，组织起源可能影响 iPS 细胞分化为特定细胞类型（如软骨细胞）的命运潜能。因此，我们生成了新的细胞工具，用于鉴定驱动重编程细胞高软骨形成潜能的固有特征。
