Generation of Human Induced Pluripotent Stem Cells from Umbilical Cord Matrix and Amniotic Membrane Mesenchymal Cells

• Published in: The Journal of biological chemistry 2010-04, Vol.285 (15), p.11227-11234
• Main Authors: Cai, Jinglei, Li, Wen, Su, Huanxing, Qin, Dajiang, Yang, Jiayin, Zhu, Fan, Xu, Jianyong, He, Wenzhi, Guo, Xiangpeng, Labuda, Krystyna, Peterbauer, Anja, Wolbank, Susanne, Zhong, Mei, Li, Zhiyuan, Wu, Wutian, So, Kwok-Fai, Redl, Heinz, Zeng, Lingwen, Esteban, Miguel Angel, Pei, Duanqing
• Format: Article
• Language: English
• Subjects: Amnion - metabolism; Animals; Cell Biology; Cell Culture Techniques - methods; Cell Differentiation; Cell Line; Cells, Cultured - cytology; Gene Expression Regulation; General Transcription Factors; Humans; Induced Pluripotent Stem (iPS) Cell; Karyotyping; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; Models, Biological; Motor Neurons - metabolism; Neurodifferentiation; Patch-Clamp Techniques; Placenta; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Reprogramming; Signal Transduction; Stem Cell; Umbilical Cord - cytology; Umbilical Cord - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.086389

The umbilical cord and placenta are extra-embryonic tissues of particular interest for regenerative medicine. They share an early developmental origin and are a source of vast amounts of cells with multilineage differentiation potential that are poorly immunogenic and without controversy. Moreover, these cells are likely exempt from incorporated mutations when compared with juvenile or adult donor cells such as skin fibroblasts or keratinocytes. Here we report the efficient generation of induced pluripotent stem cells (iPSCs) from mesenchymal cells of the umbilical cord matrix (up to 0.4% of the cells became reprogrammed) and the placental amniotic membrane (up to 0.1%) using exogenous factors and a chemical mixture. iPSCs from these 2 tissues homogeneously showed human embryonic stem cell (hESC)-like characteristics including morphology, positive staining for alkaline phosphatase, normal karyotype, and expression of hESC-like markers including Nanog, Rex1, Oct4, TRA-1–60, TRA-1–80, SSEA-3, and SSEA-4. Selected clones also formed embryonic bodies and teratomas containing derivatives of the 3 germ layers, and could as well be readily differentiated into functional motor neurons. Among other things, our cell lines may prove useful for comparisons between iPSCs derived from multiple tissues regarding the extent of the epigenetic reprogramming, differentiation ability, stability of the resulting lineages, and the risk of associated abnormalities.