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EMBRYONIC STEM CELLS

Derivation of Euploid Human Embryonic Stem Cells from Aneuploid Embryos

^aThe International Stem Cell Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA;
^bDepartment of Genetics, The Institute of Life Sciences, The Hebrew University, Jerusalem, Israel;
^cART Reproductive Center, Beverly Hills, California, USA

Key Words. Human embryonic stem cells • Derivation • Preimplantation genetic diagnosis • Preimplantation genetic screening • Aneuploid • Mosaic

Correspondence: Correspondence: Neta Lavon, Ph.D., The International Stem Cell Research Institute, Cedars-Sinai Medical Center, Davis Building, Room 2008, 8700 Beverly Boulevard, Los Angeles, California, USA. Telephone: 310-423-7626; Fax: 310-423-1651; e-mail: lavonn{at}cshs.org

Received on February 15, 2008; accepted for publication on April 22, 2008.

First published online in STEM CELLS EXPRESS  May 1, 2008.

Human embryonic stem cells (HESCs) are pluripotent cells derived from the inner cell mass of preimplantation embryos. In this study, to isolate new lines of HESCs, we used blastocyst-stage embryos diagnosed as aneuploid in preimplantation genetic screening (PGS). During in vitro fertilization treatments, PGS is widely applied to identify chromosomal aneuploidies, especially in cases of advanced maternal age. Embryos that are detected as carrying aneuploidies are destined to be discarded unless donated for research. From 74 fresh PGS-defined aneuploid embryos, we derived seven HESC lines. Most of the embryos were left to hatch spontaneously through the hole created for blastomere biopsy and further treated by immunosurgery. The seven HESC lines exhibited morphology and markers typical of HESCs and the capacity for long-term proliferation. The derived HESC lines manifested pluripotent differentiation potential both in vivo and in vitro. Surprisingly, karyotype analysis of the HESC lines that were derived from these aneuploid embryos showed that the cell lines carry a normal euploid karyotype. We show that the euploidy was not achieved through chromosome duplication. Alternatively, we suggest that the euploid HESC lines originated from mosaic embryos consisting of aneuploid and euploid cells, and in vitro selection occurred to favor euploid cells. We assume that aneuploid HESC lines could be isolated mostly from embryos that are uniform for the aneuploidy. These results led us to conclude that the aneuploid mosaic embryos that are destined to be discarded can serve as an alternative source for normal euploid HESC lines.

Disclosure of potential conflicts of interest is found at the end of this article.

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