Teratoma formation and hepatocyte differentiation in mouse liver transplanted with mouse embryonic stem cell–derived embryoid bodies

Teramoto, Koji; Hara, Yuzuru; Kumashiro, Yuji; Chinzei, Ryoko; Tanaka, Yujiro; Shimizu-Saito, Keiko; Asahina, Kinji; Teraoka, Hirobumi; Arii, Shigeki

doi:10.1016/j.transproceed.2004.12.120

Cited by 51 publications

(31 citation statements)

References 3 publications

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“…The formation of a teratoma from differentiated mouse ESCs implies that despite the presence of differentiated cartilaginous tissue, cells capable of forming teratomas still exist in these constructs. This was also observed after injection of 9-15 day old EB cells that were differentiated into the hepatocyte lineage, implying that undifferentiated cells are still present in these cultures [212]. Besides differentiation status of the ESC-derived cells, the high numbers of implanted cells might stimulate teratoma formation [212,213].…”

Section: Ebcell Ebsmentioning

confidence: 76%

“…This was also observed after injection of 9-15 day old EB cells that were differentiated into the hepatocyte lineage, implying that undifferentiated cells are still present in these cultures [212]. Besides differentiation status of the ESC-derived cells, the high numbers of implanted cells might stimulate teratoma formation [212,213]. The site of injection [212] or implantation also plays a role in the formation of a teratoma.…”

Section: Ebcell Ebsmentioning

confidence: 77%

“…Besides differentiation status of the ESC-derived cells, the high numbers of implanted cells might stimulate teratoma formation [212,213]. The site of injection [212] or implantation also plays a role in the formation of a teratoma. In an experiment by Wakitani et al, the injection of undifferentiated mouse ESCs into the knee joint resulted in less tumor formation than subcutaneous implantation [162].…”

Section: Ebcell Ebsmentioning

confidence: 99%

“…Implantation in the tissue of interest does not prevent teratoma formation of undifferentiated ESCs, as observed when ESCs were injected into the heart [245,246] or liver [212]. Mouse ESC injected into a mouse joint formed teratomas and destroyed the joint, although the incidence was lower and teratomas were smaller than teratomas developing after subcutaneous injection [162].…”

Section: Teratoma Formationmentioning

confidence: 99%

See 3 more Smart Citations

Skeletal tissue engineering using embryonic stem cells

Jukes

Blitterswijk

Boer

2010

J Tissue Eng Regen Med

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Section: Ebcell Ebsmentioning

confidence: 76%

Section: Ebcell Ebsmentioning

confidence: 77%

Section: Ebcell Ebsmentioning

confidence: 99%

Section: Teratoma Formationmentioning

confidence: 99%

See 2 more Smart Citations

Skeletal tissue engineering using embryonic stem cells

Jukes

Blitterswijk

Boer

2010

J Tissue Eng Regen Med

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“…Therefore, one of the problems faced while using ES and iPS cell-derived cells for transplantation into patients is the risk of tumorigenicity [5]. For example, transplantation of mouse hepatocytes differentiated from ES cells into liver resulted in the formation of teratoma [16]. Tumorigenicity was initially attributed to genomic integration of the viral vectors used for the induction of pluripotency [17].…”

Section: Pluripotency and Tumorigenicitymentioning

confidence: 99%

Hepatocyte Selection Medium

Tomizawa¹,

Shinozaki²,

Motoyoshi³

et al. 2014

Pluripotent Stem Cell Biology - Advances in Mechanisms, Methods and Models

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Reemergence of undifferentiated cells from transplants of human induced pluripotent stem cells is a possible potential risk factor of tumorigenic differentiation

et al. 2013

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Although induced pluripotent stem cells (iPSCs) are a potential source for transplantation therapy, malignant transformation (tumourigenesis) remains a major concern in their safe clinical application. iPSCs are considered more tumourigenic than embryonic stem cells (ESCs) because of genetic and epigenetic manipulations. We generated 22 human iPSC lines from normal human fibroblasts and injected three of these cell lines into SCID mice, and produced three tumours, all of which were identified as teratomas with at least two germ layers. Using cells cultured from them, RT-PCR showed that the cells expressed undifferentiated cell markers, including OCT4 and NANOG. This suggests that some undifferentiated cells remain in the teratoma during its formation. We also found emergence of cells expressing undifferentiated cell markers from teratoma-derived cells during culturing with the ESC medium. Immunocytochemical analyses showed that NANOG-, OCT4-and SSEA4-positive cells appeared and increased with time in culture. These data indicate that iPSC-like undifferentiated cells can emerge from differentiated cells under certain condition and they may present a potential risk of tumourigenesis, as do residual iPSCs.Re-emergence of undifferentiated cells T. Kumazaki et al.

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Teratoma formation and hepatocyte differentiation in mouse liver transplanted with mouse embryonic stem cell–derived embryoid bodies

Cited by 51 publications

References 3 publications

Skeletal tissue engineering using embryonic stem cells

Skeletal tissue engineering using embryonic stem cells

Hepatocyte Selection Medium

Reemergence of undifferentiated cells from transplants of human induced pluripotent stem cells is a possible potential risk factor of tumorigenic differentiation

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