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

Abstract

Abstract. Embryonic stem (ES) cells are used in cell therapy and tissue engineering due to their ability to produce different cells types. However, studies of ES cells that are derived from fertilized embryos have raised concerns about the limitations imposed by ethical and political considerations. Therefore, many studies of stem cells use the stem cells that are derived from unfertilized oocytes and adult tissue. Although parthenogenetic embryonic stem (ESP) cells also avoid ethical and political dilemmas and can be used in cell-based therapy, the ESP cells exhibit growth retardation problems. Therefore, to investigate the potential for muscle growth from genetically modified ESP cells, we established four ES cell types, including normal embryonic stem (ESN) cells, ESP cells, ESP cells that overexpress the insulin-like growth factor 2 (Igf2) gene (ESI) and ESP cells with down-regulated H19 gene expression (ESH). Using these cells, we examined the expression profiles of genes that were related to imprinting and muscle using microarrays. The gene expression patterns of ESI and ESH cells were similar and were more closely related to the ESN pattern than that of the ESP cells. Differentiated ESH cells exhibited increased expression of bone morphologic protein 4 (BMP4), which is a mesoderm marker, compared with the differentiated ESI cells. We showed that Igf2 expression was induced by H19 silencing in the ESP cells via hypermethylation of the H19 imprinting control region 1 (ICR1). Moreover, the proportion of ESH-derived chimera was slightly higher than those produced from the ESP cells. In addition, we detected increased cell proliferation in the MEF cells following H19 knock-down. These results indicate that the ESH cells may be a source of cell-based therapy for conditions such as muscular atrophy.

Could lncRNAs be the Missing Links in Control of Mesenchymal Stem Cell Differentiation?

“…One very interesting study performed a knockdown of H19 in embryonic stem cells (ESCs) and demonstrated the possibility of using modified stem cells as a cell-based therapy for conditions such as muscular atrophy (Kwak et al 2012). …”

Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injury

“…However, due to issues such as immune rejection, tumorigenicity, and ethics, the application of ESCs in clinical treatment is limited [ 13 ]. To avoid the ethics issue, several alternative sources have been reported, such as therapeutic cloning [ 14 , 15 ], parthenogenetic ES cells [ 16 , 17 ], and induced pluripotent stem cells (iPSCs) [ 18 , 19 ]. However, their tumorigenic potential also limit the clinical application of pluripotent stem cells [ 20 , 21 ].…”