Establishment of Human cell Type-Specific iPS cells with Enhanced Chondrogenic Potential

被引:32
作者
Guzzo, Rosa M. [1 ,3 ]
Scanlon, Vanessa [1 ]
Sanjay, Archana [1 ]
Xu, Ren-He [2 ,3 ]
Drissi, Hicham [1 ,2 ,3 ]
机构
[1] Univ Connecticut, Ctr Hlth, Dept Orthopaed Surg, Farmington, CT 06030 USA
[2] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA
[3] Univ Connecticut, Ctr Hlth, Stem Cell Inst, Farmington, CT 06030 USA
关键词
Human induced pluripotent stem cells; Chondrogenic differentiation; Reprogramming; Articular cartilage; Cord blood; PLURIPOTENT STEM-CELLS; EPIGENETIC MEMORY; DIFFERENTIATION; GENERATION; LINEAGE;
D O I
10.1007/s12015-014-9538-8
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:820 / 829
页数:10
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