Generation of insulin-expressing cells from mouse embryonic stem cells

Milne, Helen M.; Burns, Christopher J.; Kitsou-Mylona, Isidora; Luther, Melanie J.; Minger, Stephen; Persaud, Shanta J.; Jones, Peter M.

doi:10.1016/j.bbrc.2004.12.183

Cited by 20 publications

(7 citation statements)

References 29 publications

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“…A recent study suggested that mouse ES cells readily differentiate into extra-embryonic endoderm in vitro, raising the possibility that the insulin-producing cells might be extra-embryonic endoderm rather than the assumed authentic embryonic endodermal endocrine cells [64]. Another report also showed that the immunoreactivity to insulin results from the uptake of exogenous insulin in vitro rather than from the differentiated cells themselves [65].…”

Section: Differentiation Of Embryonic Stem (Es) Cells Into Insulin-prmentioning

confidence: 99%

Identification and expansion of pancreatic stem/progenitor cells

2005

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Pancreatic islet transplantation represents an attractive approach for the treatment of diabetes. However, the limited availability of donor islets has largely hampered this approach. In this respect, the use of alternative sources of islets such as the ex vivo expansion and differentiation of functional endocrine cells for treating diabetes has become the major focus of diabetes research. Adult pancreatic stem cells/progenitor cells have yet to be recognized because limited markers exist for their identification. While the pancreas has the capacity to regenerate under certain circumstances, questions where adult pancreatic stem/progenitor cells are localized, how they are regulated, and even if the pancreas harbors a stem cell population need to be resolved. In this article, we review the recent achievements both in the identification as well as in the expansion of pancreatic stem/progenitor cells.

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Section: Differentiation Of Embryonic Stem (Es) Cells Into Insulin-prmentioning

confidence: 99%

Identification and expansion of pancreatic stem/progenitor cells

2005

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“…When mESCs are cultured with mouse embryonic fibroblast, feeder cells, they proliferate indefinitely and retain the potential to differentiate into various lineages of all three primary germ layers (Martin, 1981). Various studies conducted to differentiate mESCs into neuronal cells, cardiomyocytes, muscle cells, and insulin secreting cells (He et al, 2005;Milne et al, 2005;Wei et al, 2005). Mesenchymal stem cells (MSCs) isolated from adult bone marrow are multipotent cells and can be differentiate into cartilage, tendon, fat, or bone marrow stroma (Woodbury et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Dynamic changes of gangliosides expression during the differentiation of embryonic and mesenchymal stem cells into neural cells

Kwak

Yu²,

Kim³

et al. 2006

Exp Mol Med

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Stem cells are used for the investigation of developmental processes at both cellular and organism levels and offer tremendous potentials for clinical applications as an unlimited source for transplantation. Gangliosides, sialic acid-conjugated glycosphingolipids, play important regulatory roles in cell proliferation and differentiation. However, their expression patterns in stem cells and during neuronal differentiation are not known. Here, we investigated expression of gangliosides during the growth of mouse embryonic stem cells (mESCs), mesenchymal stem cells (MSCs) and differentiated neuronal cells by using high-performance thin-layer chromatography (HPTLC). Monosialoganglioside 1 (GM1) was expressed in mESCs and MSCs, while GM3 and GD3 were expressed in embryonic bodies. In the 9-day old differentiated neuronal cells from mESCs cells and MSCs, GM1 and GT1b were expressed. Results from immunostaining were consistent with those observed by HPTLC assay. These suggest that gangliosides are specifically expressed according to differentiation of mESCs and MSCs into neuronal cells and expressional difference of gangliosides may be a useful marker to identify differentiation of mESCs and MSCs into neuronal cells.

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“…Some of these protocols have reported the derivation of neuronal phenotypes [4,5,8,[17][18][19] within differentiated populations whereas a more recent publication has suggested that ES-derived insulin-positive cells are actually extra-embryonic in origin [20]. In light of these findings, we undertook to investigate the nature of the cells as well as develop another means of establishing the presence of de novo synthesized insulin.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, authors have reported that ES-derived populations expressing insulin, and in some cases C-peptide, are devoid of granules typically found in beta-cells and are mostly apoptotic [18] and that insulin is released artifactually from differentiated ES cells [19]. The presence of neuronal-like phenotypes within the differentiated ES cultures [18] and the suggestion that insulin-positive cells may be extra-embryonic in origin [20] has also highlighted the need for stringent criteria to define true beta-cell identity. This may include: (a) measuring transcript expression of beta-cell associated genes as well as genes associated with other lineages, (b) measuring expression of key beta-cell marker proteins and (c) demonstrating functional de novo insulin synthesis.…”

Section: Introductionmentioning

confidence: 99%

Detecting de novo insulin synthesis in embryonic stem cell-derived populations

Kiernan

Barron

O’Sullivan

et al. 2007

Experimental Cell Research

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Several studies in recent years have described protocols, both genetic-and culture-based, that induce the differentiation of embryonic stem (ES) cells towards a pancreatic beta-cell type. The success of previous protocols in generating insulin-producing beta-cells has been questioned due in part to uncertainty regarding cell lineage but also due to the controversy regarding the source of any insulin detected in these cells. In an attempt to address the latter, we designed a novel assay that can identify de novo insulin synthesis.The method is based on metabolic labeling combined with a modified radioimmunoassay and will routinely detect less than 5 pg/μl of de novo insulin synthesis in lysates from the insulinoma cell line MIN6. This assay failed to detect any newly translated insulin in an ES cell-derived population generated using an adapted version of a previously published, 5-stage differentiation protocol. In combination with other techniques, including immunofluorescent staining and western blot analysis to detect and quantify C-peptide, we conclude that the majority of the insulin found in these differentiated ES cell cultures is medium-derived.

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Generation of insulin-expressing cells from mouse embryonic stem cells

Cited by 20 publications

References 29 publications

Identification and expansion of pancreatic stem/progenitor cells

Identification and expansion of pancreatic stem/progenitor cells

Dynamic changes of gangliosides expression during the differentiation of embryonic and mesenchymal stem cells into neural cells

Detecting de novo insulin synthesis in embryonic stem cell-derived populations

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