Clinically failed eggs as a source of normal human embryo stem cells.
The promise of human embryo stem cells (hESCs) for regenerative medicine is offset by the ethical and practical challenges involved in sourcing eggs and embryos for this objective. In this study we sought to isolate an hESC line from clinically failed eggs, the usage of which would not conflict with donor interests to conceive. A total of 8 blastocysts were allocated for hESC derivation from a pool of 579 eggs whose fertilization had been clinically assessed to have occurred abnormally (i.e., three pronuclei) or failed (i.e., no pronuclei) following in vitro insemination or intracytoplasmic sperm injection (ICSI). The latter were subjected to a recovery intervention consisting of either reinsemination by ICSI or parthenogenetic stimulation. One hESC line (RCM1) was obtained from a failed-to-fertilize inseminated egg recovered by parthenogenetic activation. Standard in vitro and in vivo characterization revealed this line to possess all of the properties attributed to a normal euploid hESC line. Whole-genome single-nucleotide polymorphism analysis further revealed that the line was biparental, indicating that sperm penetration had occurred, although parthenogenetic stimulation was required for activation. Our results demonstrate the viability of an alternative strategy to generate normal hESC lines from clinically failed eggs, thereby further minimizing the potential to conflict with donor reproductive interest to conceive.
De Sousa
Paul A
PA
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4SB, UK. paul.desousa@ed.ac.uk
Gardner
John
J
Sneddon
Sharon
S
Pells
Steve
S
Tye
Britt Jorgensen
BJ
Dand
Pawlina
P
Collins
Daniel M
DM
Stewart
Karen
K
Shaw
Lisa
L
Przyborski
Stefan
S
Cooke
Michael
M
McLaughlin
K John
KJ
Kimber
Susan J
SJ
Lieberman
Brian A
BA
Wilmut
Ian
I
Brison
Daniel R
DR
D001755:Blastocyst / Q000166:cytology; D002877:Chromosomes, Human; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D006579:Heterozygote; D006801:Humans; D015053:Zygote / Q000166:cytology*