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Embryonic stem (ES) cells are used in cell therapy and tissue engineeringdue to their ability to produce different cells types. However, studies of EScells that are derived from fertilized embryos have raised concerns about thelimitations imposed by ethical and political considerations. Therefore, many studiesof stem cells use the stem cells that are derived from unfertilized oocytes andadult tissue. Although parthenogenetic embryonic stem (ESP) cells also avoid ethicaland political dilemmas and can be used in cell-based therapy, the ESP cells exhibitgrowth retardation problems. Therefore, to investigate the potential for musclegrowth from genetically modified ESP cells, we established four ES cell types,including normal embryonic stem (ESN) cells, ESP cells, ESP cells that overexpressthe insulin-like growth factor 2 (Igf2) gene (ESI) and ESP cells with down-regulatedH19 gene expression (ESH). Using these cells, we examined the expression profilesof genes that were related to imprinting and muscle using microarrays. The geneexpression patterns of ESI and ESH cells were similar and were more closely relatedto the ESN pattern than that of the ESP cells. Differentiated ESH cells exhibitedincreased expression of bone morphologic protein 4 (BMP4), which is a mesodermmarker, compared with the differentiated ESI cells. We showed that Igf2 expressionwas induced by H19 silencing in the ESP cells via hypermethylation of the H19imprinting control region 1 (ICR1). Moreover, the proportion of ESH-derived chimerawas slightly higher than those produced from the ESP cells. In addition, we detectedincreased cell proliferation in the MEF cells following H19 knock-down. Theseresults indicate that the ESH cells may be a source of cell-based therapy forconditions such as muscular atrophy.

Parthenogenetic embryonic stem cells with H19 siRNA-mediated knockdown as a potential resource for cell therapy