核型正常和异常的人胚胎干细胞系来源于pgd分析的胚胎。

Teija Peura, Alexis Bosman, Omar Chami, Robert P S Jansen, Katka Texlova, Tomas Stojanov
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引用次数: 45

摘要

虽然正常核型通常是干细胞系的必要条件,但具有明确染色体非整倍体的干细胞可能会出现新的应用。因此,我们研究了使用活检发现的非整倍体胚胎,然后使用荧光原位杂交(FISH)进行着床前遗传学诊断(PGD),以及发育受阻的胚胎进行干细胞衍生。从36个培养的41个胚胎中获得11个干细胞系,经pgd分析的发育成熟胚胎(45%)的成功率高于临床不适合的非pgd胚胎(13%)。由此产生的干细胞系进行了核型分析,令人惊讶的是,来自非整倍体胚胎的9个系中有6个系以及来自非pgd胚胎的2个系的核型正常。来自PGD胚胎的3个细胞系为非整倍体,分别表现为5三体、16三体和13同染色体。所有非整倍体系均未出现与原始PGD分析相同的异常。我们的研究有三个重要的含义。首先,我们证实了从pgd测试的胚胎以及发育异常的胚胎中产生干细胞系的能力,为临床重要的非整倍体研究提供了特殊的干细胞系。其次,我们观察到,干细胞从明显的非整倍体胚胎衍生出来,往往受到潜在的嵌合和核型正常细胞的干细胞系的新兴优势的阻碍。然而,其必然结果是,从发育异常的普通胚胎中产生正常的干细胞系,为干细胞提供了一个新的胚胎来源,无论是用于研究还是最终用于捐赠家庭的治疗用途。
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Karyotypically normal and abnormal human embryonic stem cell lines derived from PGD-analyzed embryos.

Although a normal karyotype is generally a requirement for stem cell lines, new applications are likely to emerge for stem cells with defined chromosomal aneuploidies. We therefore investigated the use of embryos found to be aneuploid on biopsy followed by preimplantation genetic diagnosis (PGD) with fluorescent in situ hybridization (FISH), and developmentally arrested embryos for stem cell derivation. Eleven stem cell lines were obtained from 41 embryos in 36 cultures, with higher success rate achieved from PGD-analyzed, developmentally advanced embryos (45%) than from clinically unsuitable non-PGD embryos (13%). The resulting stem cell lines were karyotyped, and surprisingly, six of the nine lines from aneuploid embryos as well as both lines from non-PGD embryos were karyotypically normal. Three lines from PGD embryos were aneuploid exhibiting trisomy 5, trisomy 16, and an isochromosome 13, respectively. None of the aneuploid lines presented the same anomally as the original PGD analysis. Our study has three important implications. First, we confirm the ability to produce stem cell lines from PGD-tested embryos as well as developmentally abnormal embryos, offering specialty stem cell lines for research into the clinically important aneuploidies. Second, we observe that stem cell derivation from apparently aneuploid embryos is often thwarted by underlying mosaicism and emerging dominance of the stem cell line by karyotypically normal cells. The corollary, however, is that regular production of normal stem cell lines from developmentally abnormal embryos ordinarity discarded opens a new source of embryos for stem cells, whether for research or for eventual therapeutic use within the donating families.

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