Suppression of malignancy by Smad3 in mouse embryonic stem cell formed teratoma

Chen, Ying; Meng, Xiao-ming; Kwok, Ka Yin; Huang, Xiao‐Ru; Choy, Kwong Wai; Wang, Chi Chiu; Lan, Hui‐Yao; Yuan, Ping

doi:10.1007/s12015-013-9452-5

Cited by 15 publications

(25 citation statements)

References 33 publications

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“…It has also been documented that SMAD3 is the mediator of signals from the TGFβ superfamily, which controls cell proliferation, pluripotency, and differentiation [70]. Recently, it has been reported that SMAD3 is closely connected with teratoma formation from ESCs [71]. SMAD3 expression was down-regulated (Fig 7E and 7F).…”

Section: Discussionmentioning

confidence: 74%

Microarray analysis of embryo-derived bovine pluripotent cells: The vulnerable state of bovine embryonic stem cells

2017

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Although there are many studies about pluripotent stem cells, little is known about pluripotent pathways and the difficulties of maintaining the pluripotency of bovine cells in vitro. Here, we investigated differently expressed genes (DEG) in bovine embryo-derived stem-like cells (eSLCs) from various origins to validate their distinct characteristics of pluripotency and differentiation. We identified core pluripotency markers and additional markers which were not determined as pluripotency markers yet in bovine eSLCs. Using the KEGG database, TGFβ, WNT, and LIF signaling were related to the maintenance of pluripotency. In contrast, some DEGs related to the LIF pathway were down-regulated, suggesting that reactivation of the pathway may be required for the establishment of true bovine embryonic stem cells (ESCs). Interestingly, oncogenes were co-down-regulated, while tumor suppressor genes were co-up-regulated in eSLCs, implying that this pattern may induce abnormal teratomas. These data analyses of signaling pathways provide essential information on authentic ESCs in addition to providing evidence for pluripotency in bovine eSLCs.

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Section: Discussionmentioning

confidence: 74%

Microarray analysis of embryo-derived bovine pluripotent cells: The vulnerable state of bovine embryonic stem cells

2017

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“…A number of studies (Thomson et al, 1998;Wakitani et al, 2003;Stojkovic et al, 2005;Nussbaum et al, 2007;Dressel et al, 2008;Prokhorova et al, 2009;Zhang et al, 2012;Li et al, 2013;Lukovic et al, 2013) have shown the potential of ESCs to form teratomas by injecting undifferentiated ESCs into mice. Most studies used immunodeficient hosts such as severe combined immunodeficient (SCID) mice (Thomson et al, 1998;Wakitani et al, 2003;Stojkovic et al, 2005;Zhang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, in many previous studies, the use of injected ESCs was associated with the risk of teratoma development (Wakitani et al, 2003;Baharvand and Matthaei, 2004;Przyborski, 2005;Nussbaum et al, 2007;Dressel et al, 2008;Prokhorova et al, 2009;Zhang et al, 2012;Li et al, 2013). In a clinical setting, this is a critical limitation of such a treatment.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, much interest among the scientific community has been on the understanding of these processes. Most studies have used immunodeficient recipient mice into which these cells were implanted (Wakitani et al, 2003;Baharvand and Matthaei, 2004;Przyborski, 2005;Nussbaum et al, 2007;Dressel et al, 2008;Prokhorova et al, 2009;Li et al, 2013). The resultant teratomas consisted of all three germ layers (ectoderm, mesoderm, endoderm) representing all tissue types in a whole individual (Prokhorova et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Teratoma Formation in Immunocompetent Mice After Syngeneic and Allogeneic Implantation of Germline Capable Mouse Embryonic Stem Cells

Aldahmash

Atteya²,

Elsafadi³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Embryonic stem cells (ESCs) have the potential to form teratomas when implanted into immunodeficient mice, but data in immunocompetent mice are limited. We therefore investigated teratoma formation after implantation of three different mouse ESC (mESC) lines into immunocompetent mice. Materials and Methods: BALB/c mice were injected with three highly germline competent mESCs (129Sv, BALB/c and C57BL/6) subcutaneously or under the kidney capsule. After 4 weeks, mice were euthanized and examined histologically for teratoma development. The incidence, size and composition of teratomas were compared using Pearson Chi-square, t-test for dependent variables, one-way analysis of variance and the nonparametric KruskalWallis analysis of variance and median test. Results: Teratomas developed from all three cell lines. The incidence of formation was significantly higher under the kidney capsule compared to subcutaneous site and occurred in both allogeneic and syngeneic mice. Overall, the size of teratoma was largest with the 129Sv cell line and under the kidney capsule. Diverse embryonic stem cell-derived tissues, belonging to the three embryonic germ layers, were encountered, reflecting the pluripotency of embryonic stem cells. Most commonly represented tissues were nervous tissue, keratinizing stratified squamous epithelium (ectoderm), smooth muscle, striated muscle, cartilage, bone (mesoderm), and glandular tissue in the form of gut-and respiratory-like epithelia (endoderm). Conclusions: ESCs can form teratomas in immunocompetent mice and, therefore, removal of undifferentiated ESC is a pre-requisite for a safe use of ESC in cell-based therapies. In addition the genetic relationship of the origin of the cell lines to the ability to transplant plays a major role.

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“…Oct4‐GFP transgene male mice were crossed with C57‐BL/6 female mice and E3.5 blastocysts were harvested from the uterus of female mouse. The blastocysts were then seeded on mitomycin‐C inactivated MEF feeder in ES medium (Schoonjans et al, ; Hayashi et al, ; Li et al, , ). ICM outgrowth was formed 6 days later.…”

Section: Methodsmentioning

confidence: 99%

Differentiation of female Oct4‐GFP embryonic stem cells into germ lineage cells

Ma¹,

Sun

Sun³

et al. 2018

Cell Biology International

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Due to high infertility ratio nowadays, it is essential to explore efficient ways of enhancing mammalian reproductivity, in particular female reproductivity. Using female Oct4-GFP embryonic stem cells, we mimic the in vivo development procedure to induce ES cells into epiblast cell-like cells (EpiLCs) and then primordial germ cell-like cells (PGCLCs). GFP positive PGCLCs that showed typical PGC markers and epigenetic modification were efficiently obtained. Further transplantation of the GFP positive PGCLC and native ovary cell mixture into ovary of infertile mice revealed that both MVH and GFP positive cells could be developed in ovary, but no later developmental stage germ cells were observed. This study suggested that Oct4-GFP ES cells may be only suitable for tracing early germ cell development.

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Suppression of malignancy by Smad3 in mouse embryonic stem cell formed teratoma

Cited by 15 publications

References 33 publications

Microarray analysis of embryo-derived bovine pluripotent cells: The vulnerable state of bovine embryonic stem cells

Microarray analysis of embryo-derived bovine pluripotent cells: The vulnerable state of bovine embryonic stem cells

Teratoma Formation in Immunocompetent Mice After Syngeneic and Allogeneic Implantation of Germline Capable Mouse Embryonic Stem Cells

Differentiation of female Oct4‐GFP embryonic stem cells into germ lineage cells

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