Tumorigenic and Differentiation Potentials of Embryonic Stem Cells Depend on TGFβ Family Signaling: Lessons from Teratocarcinoma Cells Stimulated to Differentiate with Retinoic Acid
A significant challenge for the development of safe pluripotent stem cell-based therapies is the incomplete in vitro differentiation of the pluripotent stem cells and the presence of residual undifferentiated cells initiating teratoma development after transplantation in recipients. To understand th...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/7284872 |
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| author | Olga Gordeeva Sergey Khaydukov |
| author_facet | Olga Gordeeva Sergey Khaydukov |
| author_sort | Olga Gordeeva |
| collection | DOAJ |
| description | A significant challenge for the development of safe pluripotent stem cell-based therapies is the incomplete in vitro differentiation of the pluripotent stem cells and the presence of residual undifferentiated cells initiating teratoma development after transplantation in recipients. To understand the mechanisms of incomplete differentiation, a comparative study of retinoic acid-induced differentiation of mouse embryonic stem (ES) and teratocarcinoma (EC) cells was conducted. The present study identified differences in proliferative activity, differentiation, and tumorigenic potentials between ES and EC cells. Higher expression of Nanog and Mvh, as well as Activin A and BMP4, was found in undifferentiated ES cells than in EC cells. However, the expression levels of Activin A and BMP4 increased more sharply in the EC cells during retinoic acid-induced differentiation. Stimulation of the Activin/Nodal and BMP signaling cascades and inhibition of the MEK/ERK and PI3K/Act signaling pathways resulted in a significant decrease in the number of Oct4-expressing ES cells and a loss of tumorigenicity, similar to retinoic acid-stimulated EC cells. Thus, this study demonstrates that a differentiation strategy that modulates prodifferentiation and antiproliferative signaling in ES cells may be effective for eliminating tumorigenic cells and may represent a valuable tool for the development of safe stem cell therapeutics. |
| format | Article |
| id | doaj-art-f57fac40e78f4f3d8f7099747306bfe7 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
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| series | Stem Cells International |
| spelling | doaj-art-f57fac40e78f4f3d8f7099747306bfe72025-02-03T07:24:22ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/72848727284872Tumorigenic and Differentiation Potentials of Embryonic Stem Cells Depend on TGFβ Family Signaling: Lessons from Teratocarcinoma Cells Stimulated to Differentiate with Retinoic AcidOlga Gordeeva0Sergey Khaydukov1Kol’tsov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov Street, Moscow 119334, RussiaShemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street 16/10, Moscow 117997, RussiaA significant challenge for the development of safe pluripotent stem cell-based therapies is the incomplete in vitro differentiation of the pluripotent stem cells and the presence of residual undifferentiated cells initiating teratoma development after transplantation in recipients. To understand the mechanisms of incomplete differentiation, a comparative study of retinoic acid-induced differentiation of mouse embryonic stem (ES) and teratocarcinoma (EC) cells was conducted. The present study identified differences in proliferative activity, differentiation, and tumorigenic potentials between ES and EC cells. Higher expression of Nanog and Mvh, as well as Activin A and BMP4, was found in undifferentiated ES cells than in EC cells. However, the expression levels of Activin A and BMP4 increased more sharply in the EC cells during retinoic acid-induced differentiation. Stimulation of the Activin/Nodal and BMP signaling cascades and inhibition of the MEK/ERK and PI3K/Act signaling pathways resulted in a significant decrease in the number of Oct4-expressing ES cells and a loss of tumorigenicity, similar to retinoic acid-stimulated EC cells. Thus, this study demonstrates that a differentiation strategy that modulates prodifferentiation and antiproliferative signaling in ES cells may be effective for eliminating tumorigenic cells and may represent a valuable tool for the development of safe stem cell therapeutics.http://dx.doi.org/10.1155/2017/7284872 |
| spellingShingle | Olga Gordeeva Sergey Khaydukov Tumorigenic and Differentiation Potentials of Embryonic Stem Cells Depend on TGFβ Family Signaling: Lessons from Teratocarcinoma Cells Stimulated to Differentiate with Retinoic Acid Stem Cells International |
| title | Tumorigenic and Differentiation Potentials of Embryonic Stem Cells Depend on TGFβ Family Signaling: Lessons from Teratocarcinoma Cells Stimulated to Differentiate with Retinoic Acid |
| title_full | Tumorigenic and Differentiation Potentials of Embryonic Stem Cells Depend on TGFβ Family Signaling: Lessons from Teratocarcinoma Cells Stimulated to Differentiate with Retinoic Acid |
| title_fullStr | Tumorigenic and Differentiation Potentials of Embryonic Stem Cells Depend on TGFβ Family Signaling: Lessons from Teratocarcinoma Cells Stimulated to Differentiate with Retinoic Acid |
| title_full_unstemmed | Tumorigenic and Differentiation Potentials of Embryonic Stem Cells Depend on TGFβ Family Signaling: Lessons from Teratocarcinoma Cells Stimulated to Differentiate with Retinoic Acid |
| title_short | Tumorigenic and Differentiation Potentials of Embryonic Stem Cells Depend on TGFβ Family Signaling: Lessons from Teratocarcinoma Cells Stimulated to Differentiate with Retinoic Acid |
| title_sort | tumorigenic and differentiation potentials of embryonic stem cells depend on tgfβ family signaling lessons from teratocarcinoma cells stimulated to differentiate with retinoic acid |
| url | http://dx.doi.org/10.1155/2017/7284872 |
| work_keys_str_mv | AT olgagordeeva tumorigenicanddifferentiationpotentialsofembryonicstemcellsdependontgfbfamilysignalinglessonsfromteratocarcinomacellsstimulatedtodifferentiatewithretinoicacid AT sergeykhaydukov tumorigenicanddifferentiationpotentialsofembryonicstemcellsdependontgfbfamilysignalinglessonsfromteratocarcinomacellsstimulatedtodifferentiatewithretinoicacid |