Derivation of human embryonic stem cell lines from embryos obtained after IVF and after PGD for monogenic disorders

Abstract

We report here on the derivation of two hES cell lines presumed to be genetically normal (VUB01 and VUB02) and three hES cell lines carrying mutations for myotonic dystrophy type 1 (VUB03_DM1), cystic fibrosis (VUB04_CF) and Huntington disease (VUB05_HD).

Diploid, but not haploid, human embryonic stem cells can be derived from microsurgically repaired tripronuclear human zygotes

“…The from eight-cell embryos; however, the derivation efficiency was poor. 39,48,49 Here, we showed a much higher efficiency of ES derivation from r2PN embryos, which would be helpful for deriving more human ES cell lines. Moreover, this approach would allow researchers more opportunities to derive human ES cells with certain diseases, such as genetic mutations and metabolic and endocrine diseases.…”

Les cellules souches embryonnaires et la pharmacologie

“…Cette capacité peut se décliner de deux façons, selon que l'on fait appel à un modèle physiologique ou pathologique pour l'identification de cibles thérapeutiques et/ou [9,10] (➜). Les lignées de CSEh établies à partir d'embryons porteurs d'un gène muté conduisent, en outre, à des modèles exprimant spontanément des anomalies moléculaires [11][12][13][14]. Ces lignées, actuellement au nombre d'une trentaine, ne sont disponibles que pour les maladies dépis-tées par diagnostic pré-implantatoire.…”

Human stem cells for modeling neurological disorders: Accelerating the drug discovery pipeline

“…When derived from blastocysts identified by preimplantation genetic diagnosis (PGD) as carrying congenital mutations for specific disease states [Verlinsky et al, 2005;Mateizel et al, 2006;Eiges et al, 2007;Ben-Yosef et al, 2008;Peura et al, 2008] or following genetic manipulation [Urbach et al, 2004], human ES cells afford new and relevant perspectives on human disorders. Combined with effective methods of differentiation, they should prove better than conventional mouse stem cell models for recapitulating the human phenotype, and at the very least are complementary to in vivo mouse models.…”

“…Combined with effective methods of differentiation, they should prove better than conventional mouse stem cell models for recapitulating the human phenotype, and at the very least are complementary to in vivo mouse models. Despite their potential, only a few human ES cell models of CNS diseases have been reported [Urbach et al, 2004;Verlinsky et al, 2005;Mateizel et al, 2006;Eiges et al, 2007]. Moreover, the pharmaceutical industry has been slow to adopt human ES cell-based screening despite a long standing use of in vitro cellular assays and the provision of guidelines for human ES cell research by organizations such as the National Academy of Sciences (http://www.nasonline.org/), the National Institutes of Health (http://www.nih.gov/), and the International Society of Stem Cell Research (http://www.isscr.org/).…”

“…While normal PGD-embryos can be used for assisted reproduction, mutant embryos can provide human ES cells exhibiting the same genotype and related defects [Verlinsky et al, 2005;Mateizel et al, 2006;Eiges et al, 2007;Ben-Yosef et al, 2008;Peura et al, 2008]. Once generated, cell lines can be used to decode the pathways through which mutations cause an inherited phenotype.…”