English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Although undifferentiated human embryonic stem cells (hESCs) are tumorigenic, this capacity is lost after differentiation, and hESCs are being widely investigated for applications in regenerative medicine. To engineer protection against the unintentional transplantation of undifferentiated cells, we generated hESCs carrying a construct in which the α1,3‐galactosyltransferase ( GalT ) open reading frame was transcribed from the  hTERT  promoter ( pmGT ). Because the endogenous  GalT  gene is inactive,  GalT  expression was limited to undifferentiated cells. A second chimeric construct ( pmfGT ) differed by replacement of the GalT leader sequence for that of the fucosyltransferase gene. Two subclones containing stable integrations of  pmGT  and  pmfGT  (M2 and F11, respectively) were assessed for their response to human serum containing antibodies to the Galα1‐3Galβ1‐4GlcNAc‐R (α‐gal) epitope. The low‐variegation line, M2, and to a lesser extent the more variegated line F11, were sensitive to human serum when exposed in the undifferentiated state. However, M2 cells were largely insensitive after differentiation and retained both a normal karyotype and the ability to differentiate into derivatives of the three germ layers in severe combined immunodeficient mice. These data exemplify a method of protection against residual, undifferentiated hESCs prior to engraftment and may provide ongoing immune surveillance after engraftment against dedifferentiation or against de novo tumorigenesis involving  hTERT  reactivation. Untransfected H9 cells were not sensitive to the human serum used in this study. Hence, in our system, interactions of hESCs with other circulating antibodies, such as anti‐Neu5Gc, were not observed.

Ablation of Undifferentiated Human Embryonic Stem Cells: Exploiting Innate Immunity Against the Gal α1‐3Galβ1‐4GlcNAc‐R (α‐Gal) Epitope