Derivation and characterization of the first abnormal human embryonic stem cell carrying a mutated von Hippel Lindau allele

J., De Vos; S., Assou; D., Cerecedo; L., Nadal; T., Anahory; A., Girardet; H., Dechaud; B., Klein; S., Hamamah
April 2008
Reproductive BioMedicine Online (Reproductive Healthcare Limited;Apr2008 Supplement 3, Vol. 16, pS-34
Academic Journal
Introduction: Human embryonic stem cells (ESC) have revolutionized the field of stem cells and are the proof of principle of in-vitro pluripotency. Human ESC provide great opportunities for regenerative medicine, pharmacological and toxicological investigation, and for the study of human development. So far, only a limited number of human ESC lines, representing a very small sample of the normal and pathological human genetic diversity, are available. Here, we report the derivation of a new human ESC line bearing an abnormal von Hippel Lindau (VHL) gene. Materials/Methods: A total of five human embryos were obtained after informed consent during preimplantation genetic diagnostic (PGD). Among five embryos, three achieved blastocyst stage. Hatching and isolation of the inner cell mass was carried out mechanically under a stereomicroscope. Results: One inner cell mass grew robustly in small clumps of round and tightly packed cells. This putative human ESC line was named HD90/18. Derivation conditions included the use of irradiated human foreskin fibroblasts, serum replacement and basic fibroblast growth factor (FGF). The cell line expressed pluripotency markers such as OCT4/POU5FI and stage-specific embryonic antigen-4 (SSEA-4), and formed embryoid bodies when switched to a feeder-free, FGF-free culture system. Cells were passaged every 5-8 days. HD90/18 is currently at passage 11 and is still growing. Conclusion: PGD human ESC can serve as important models of the genetic disorders that they carry. The human ESC HD90/18 is a unique model to study the molecular mechanisms underlying the pathologies associated with VHL disease.


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