Feki, A.

Hovatta, O.

Jaconi, M.

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Derivation of human embryonic stem cell lines from singlecells of 4-cell stage embryos: be aware of the risksSir,Most of the human embryonic stem cell (hESC) lines havebeen derived from the inner mass of blastocyst stageembryos, some from 8-cell stage morula (Streclchenko et al.,2004) and some from isolated blastomeres from morulae(Chung et al., 2008).In a very recent abstract, a Belgian team (Van de Veldeet al., 2008) elegantly established an embryonic stem cellline from a single blastomere isolated from a 4-cellstage embryo (from 1 out of 12 embryos). This team hada unique opportunity to establish good quality embryosfrom donated oocytes and sperm. By deriving a linefrom one blastomere, they gave evidence for the totipotencyof single cells at 4-cell stage in human embryo. The result-ing hESC line was, however, chromosomally abnormalwith a deletion in chromosome 18 and a duplication inchromosome 7.In Switzerland, the embryo research law is very strict, andobtaining good quality embryos for hESC derivation is vir-tually impossible, even though the law allows hESC deri-vation and culture. Our team recently derived a hESC line(Ch-ES1) from a frozen-thawed 4-cell stage embryo, inwhich only one blastomere survived thawing. The survivingcell grew on human foreskin feeders (Hovatta et al., 2003)and formed a hESC-like colony which has since then beenpassaged and cultured as a hESC line for over a year (Fekiet al., 2008). This line proved to be chromosomally veryabnormal, with triploidies and several deletions and dupli-cations. It forms malignant teratocarcinoma-like tumorswhen injected into SCID mice.The Belgian team has now an excellent opportunity to showhow often such lines are abnormal, a type of study still very dif-ficult in many other countries. It is not new that poor qualityembryos often have chromosomal abnormalities (Hardarsonet al., 2003), but on the other hand, we do not know yet howmuch culture conditions affect the chromosomes of earlylines, even though culture adaptation is well known (Draperet al., 2004).In this light, the interpretation of many media that deri-vation of lines from single blastomeres is ethically a moreacceptable method of derivation of hESC lines than destroy-ing whole embryos cannot be supported by the scientific com-munity. It appears that sometimes even the scientiststhemselves provoke such ideas (Chung et al., 2008). TheBelgian team has just been revealing very important biologi-cal mechanisms, but some media changed even their messageto that direction. Also in Switzerland, we have to make clearthat we now have an important tool to solve some problems incancer development, but it does not offer solutions for anyethical questions in hECS derivation. The fact that hESClines can be obtained from cells without destroying theembryo, or from cells of a ‘dead’ embryo, does not makesuch lines ethically more acceptable. Abnormality issuesshould not be underestimated.ReferencesChung Y, Klimanskaya I, Becker S, Li T, Maserati M, Lu SJ, Zdravkovic T,Ilic D, Genbacev O, Fisher S et al. Human embryonic stem cell linesgenerated without embryo destruction. Cell Stem Cell 2008;2:113–117.Draper JS, Smith K, Gokhale P, Moore HD, Maltby E, Johnson J, Meisner L,Zwaka TP, Thomson JA, Andrews PW. Recurrent gain of chromosomes 17qand 12 in cultured human embryonic stem cells. Nat Biotechnol2004;22:53–54Feki A, Bosman A, Dubuisson JB, Irion O, Dahoun S, Pelte MF, Hovatta O,Jaconi M. Derivation of a human embryonic stem cell line (ESC) from asingle blastomere of an arrested stage four embryo. Swiss Medial Weekly2008;138:540–550.Hardarson T, Caisander G, Sjogren A, Hanson C, Hamberger L, Lundin K. Amorphological and chromosomal study of blastocysts developing frommorphologically suboptimal human pre-embryos compared with controlblastocysts. Hum Reprod 2003;18:399–407.Hovatta O, Mikkola M, Gertow K, Stro¨mberg AM, Inzunza J, Hreinsson J,Anda¨ng L, Ahrlund-Richter L. A culture system using human foreskinfibroblasts as feeder cells allows production of human embryonic stemcells. Hum Reprod 2003;18:1404–1409.Streclchenko N, Verslinsky O, Kukharenko V, Verlisnky J. Morula-derivedhuman embryonic stem cell lines. Reprod Biomed Online 2004;9:623–629.Van de Velde H, Geens M, Mateiyel I, Spits C, Sermon K, De Rycke M, Vander Elst J, Devroey P, Tournaey H, Liebaers I. A human embryonic stem cellline derived from a single blastomere of a 4-cell stage embryo. ESHRE 2008,6–9 July, Barcelona. Hum Reprod Abstract O-274.A. Feki1,2, O. Hovatta2,3,5 and M. Jaconi41Laboratory of Stem Cell Research, Geneva UniversityHospitals, Geneva, Switzerland;2Department of Obstetrics and Gynecology, Geneva UniversityHospitals, Geneva, Switzerland;3Division of Obstetrics and Gynecology, Department ofClinical Sciences, Karolinska Institutet, Stockholm, Sweden and4Department of Pathology and Immunology, Faculty ofMedicine, Geneva University, Switzerland5Correspondence address. E-mail: outi.hovatta@ki.sedoi:10.1093/humrep/den369Advance Access publication on October 14, 2008Impact of hyperglycemia on early embryo developmentand embryopathy: in vitro experimentsusing a mouse modelSir,Fraser et al. (2007) identify the media they used in their workas mKSOM and KSOM, and characterize them as a ‘syntheticoviductal medium enriched with potassium’. We wish to pointout that his characterization is erroneous. A medium calledSOM was developed by Lawitts and Biggers (1991) using theexperimental strategy called ‘sequential simplex optimization’(hence SOM). SOM medium was not designed to imitate thecomposition of oviductal secretions. It was developed toovercome the 2-cell block which, at the time, interfered withmany studies on the developmental biology of the mouseembryo. KSOM was later modified by raising the potassiumconcentration in SOM (Lawitts and Biggers, 1993) based on2874Letters to the Editor

Derivation of human embryonic stem cell lines from single cells of 4-cell stage embryos: be aware of the risks

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