Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem cells.
The use of stem cells for regenerative medicine has captured the imagination of the public, with media attention contributing to rising expectations of clinical benefits. Human embryonic stem cells (hESCs) are the best model for capital investment in stem cell therapy and there is a clear need for their robust genetic characterization before scaling-up cell expansion for that purpose. We have to be certain that the genome of the starting material is stable and normal, but the limited resolution of conventional karyotyping is unable to give us such assurance. Advanced molecular cytogenetic technologies such as array comparative genomic hybridization for identifying chromosomal imbalances, and single nucleotide polymorphism analysis for identifying ethnic background and loss of heterozygosity should be introduced as obligatory diagnostic tests for each newly derived hESC line before it is deposited in national stem cell banks. If this new quality standard becomes a requirement, as we are proposing here, it would facilitate and accelerate the banking process, since end-users would be able to select the most appropriate line for their particular application, thus improving efficiency and streamlining the route to manufacturing therapeutics. The pharmaceutical industry, which may use hESC-derived cells for drug screening, should not ignore their genomic profile as this may risk misinterpretation of results and significant waste of resources.
Stephenson
Emma
E
Embryonic Stem Cell Laboratories, Guy's Assisted Conception Unit, Division of Reproduction and Endocrinology, King's College London, London, UK.
Ogilvie
Caroline Mackie
CM
Patel
Heema
H
Cornwell
Glenda
G
Jacquet
Laureen
L
Kadeva
Neli
N
Braude
Peter
P
Ilic
Dusko
D
D018929:Cell Culture Techniques; D055028:Comparative Genomic Hybridization; D046149:Embryo Culture Techniques; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation*; D042822:Genomic Instability; D006801:Humans; D007621:Karyotyping; D020641:Polymorphism, Single Nucleotide; D044968:Regenerative Medicine / Q000592:standards*
BMJ. 2005 May 21;330(7501):1159-60
15905229
Stem Cells. 2007 Sep;25(9):2215-23
17569786
Cancer Res. 2005 Jul 15;65(14):6071-9
16024607
Cell Stem Cell. 2010 Jan 8;6(1):80-9
20074536
Nat Biotechnol. 2007 Feb;25(2):207-15
17287758
Nat Biotechnol. 2007 Jul;25(7):803-16
17572666
Fertil Steril. 2005 Aug;84(2):343-55
16084875
Science. 2009 Dec 4;326(5958):1337-9
19965731
PLoS Med. 2009 Feb 17;6(2):e1000029
19226183
APMIS. 2005 Nov-Dec;113(11-12):751-5
16480447
J Cell Biochem. 2006 Oct 1;99(2):508-16
16622834
Curr Opin Cell Biol. 1998 Oct;10(5):647-53
9818176
Reproduction. 2006 Nov;132(5):691-8
17071770
Hum Reprod Update. 2007 Mar-Apr;13(2):103-20
16936306
Cytotechnology. 2008 Sep;58(1):11-6
19002774
Nat Methods. 2010 Jan;7(1):6-7
20038950
J Cell Biochem. 2008 Dec 15;105(6):1352-60
18980213
Nat Biotechnol. 2004 Jan;22(1):53-4
14661028
Regen Med. 2006 Jan;1(1):95-101
17465823
Cell Stem Cell. 2007 Nov;1(5):490-4
18938745
Ann N Y Acad Sci. 2009 Jan;1151:157-66
19154522
Science. 1997 Apr 4;276(5309):81-7
9082990
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3586-90
11891338
Prenat Diagn. 1995 Jan;15(1):41-9
7739996
Curr Biol. 1998 Jan 29;8(3):145-55
9443911
Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4783-8
15772165
Nat Biotechnol. 2001 Oct;19(10):971-4
11581665
Cloning Stem Cells. 2006;8(1):16-23
16571074
Nucleic Acids Res. 2001 Jan 1;29(1):308-11
11125122
Science. 1998 Nov 6;282(5391):1145-7
9804556
Stem Cells. 2006 Nov;24(11):2549-56
16840553
Stem Cells. 2006 Apr;24(4):800-3
16543487
Stem Cells. 2005 Feb;23(2):211-9
15671144
Hum Reprod. 2000 Sep;15(9):2003-7
10967004
Hum Mol Genet. 2008 Apr 15;17(R1):R48-53
18632697
Reproduction. 2006 Nov;132(5):681-9
17071769
Mutat Res. 2005 Feb 15;570(1):49-61
15680402
Am J Med Genet A. 2006 Dec 15;140(24):2757-67
17103431
Science. 1976 Mar 26;191(4233):1268-70
1257746
Mol Biotechnol. 2010 Nov;46(3):234-42
20524159
Nat Biotechnol. 2010 Apr;28(4):371-7
20351689
Mol Cancer. 2008 Oct 03;7:76
18834512
Nat Rev Genet. 2006 Feb;7(2):85-97
16418744
Nat Genet. 2005 Oct;37(10):1099-103
16142235
Mol Cytogenet. 2010 Apr 15;3:9
20398301
Fertil Steril. 1982 Oct;38(4):447-53
7117572
Regen Med. 2008 Jan;3(1):105-16
18154466
Nat Biotechnol. 2005 Jan;23(1):19-20
15637610
Nature. 2005 Oct 27;437(7063):1299-320
16255080
Nat Biotechnol. 2006 Feb;24(2):185-7
16388305
Nat Biotechnol. 2008 Dec;26(12):1364-6
19029913
Nucleic Acids Res. 2007 Jan;35(Database issue):D711-5
17135185
Nat Biotechnol. 2005 Jun;23(6):699-708
15940242
Fertil Steril. 1999 Nov;72(5):837-44
10560987
Cloning Stem Cells. 2005;7(3):141-53
16176124
Trends Cell Biol. 2010 Mar;20(3):170-5
20061153
Nucleic Acids Res. 2006 Jan 26;34(2):445-50
16439806
Stem Cells. 2008 Nov;26(11):2777-81
18703662
Lancet. 1983 Apr 30;1(8331):956-8
6132270
Fertil Steril. 2007 May;87(5):1053-8
17418829
Biochem Biophys Res Commun. 2006 Oct 6;348(4):1472-8
16920071
Am J Med Genet. 1980;6(2):137-43
7192492
Science. 2001 Feb 16;291(5507):1304-51
11181995
Nat Biotechnol. 2008 Dec;26(12):1361-3
19029912
Nature. 2007 Oct 18;449(7164):851-61
17943122
Lancet. 2004 Feb 7;363(9407):417-21
14962520
Regen Med. 2009 Nov;4(6):899-909
19903007
Nat Genet. 2004 Sep;36(9):949-51
15286789
Stem Cells. 2006 Oct;24(10):2162-9
16794263
PLoS One. 2010 Apr 23;5(4):e10263
20428235
Fertil Steril. 1994 Jan;61(1):111-7
8293824
N Engl J Med. 2010 Jan 14;362(2):183-5
20018958
Stem Cells Dev. 2010 Jan;19(1):39-46
19485710
Nature. 2003 Dec 18;426(6968):789-96
14685227
Nat Biotechnol. 2009 Jan;27(1):91-7
19122652
Reprod Biomed Online. 2000;1(1):17-26
12804207
Stem Cells. 2008 Jun;26(6):1484-9
18369100
Bioessays. 2000 May;22(5):452-9
10797485
Cancer Res. 2004 May 1;64(9):3060-71
15126342