Human embryonic stem cell lines with genetic disorders

Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation

“…ES cell lines with such disease-causing mutations can be generated using embryos, which in the course of in vitro fertilisation have been excluded from transfer into the uterus via preimplantation genetic diagnosis of single-gene disorders or structural and numerical chromosome aberrations. 65,66 In the recent past, also a variety of iPS lines from single-gene disorders, chromosome syndromes and complex diseases have been generated and it would be of great interest to use iPS lines from infertile men as in vitro models for germ cell formation. 67,68 However, the spectrum of usable ES cells with an inherited defect is limited, because in vitro fertilisation with preimplantation genetic diagnosis is only rarely applied.…”

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.…”

“…Once generated, cell lines can be used to decode the pathways through which mutations cause an inherited phenotype. Examples of PGD-derived ES cells representing CNS related disorders include lines for Huntington's disease [Verlinsky et al, 2005] and fragile X syndrome [Eiges et al, 2007]. Once established, these and other PGD-cell lines have the potential to provide a valuable and unlimited source of undifferentiated and differentiating ES cells and derivative neurons, glia, and other somatic cells for investigating the cause, effect, and treatment of aberrant human biology on a cellular level.…”