Journal ArticleDOI
Adaptation to culture of human embryonic stem cells and oncogenesis in vivo
Duncan Baker,Neil J. Harrison,Edna Maltby,Kath Smith,Harry Moore,Pamela J. Shaw,Paul R. Heath,Hazel Holden,Peter W. Andrews +8 more
Reads0
Chats0
TLDR
It is proposed that the changes observed in HESCs in culture reflect tumorigenic events that occur in vivo, particularly in testicular germ cell tumors, supporting a link between culture adaptation and malignancy.Abstract:
The application of human embryonic stem cells (HESCs) to provide differentiated cells for regenerative medicine will require the continuous maintenance of the undifferentiated stem cells for long periods in culture. However, chromosomal stability during extended passaging cannot be guaranteed, as recent cytogenetic studies of HESCs have shown karyotypic aberrations. The observed karyotypic aberrations probably reflect the progressive adaptation of self-renewing cells to their culture conditions. Genetic change that increases the capacity of cells to proliferate has obvious parallels with malignant transformation, and we propose that the changes observed in HESCs in culture reflect tumorigenic events that occur in vivo, particularly in testicular germ cell tumors. Further supporting a link between culture adaptation and malignancy, we have observed the formation of a chromosomal homogeneous staining region in one HESC line, a genetic feature almost a hallmark of cancer cells. Identifying the genes critical for culture adaptation may thus reveal key players for both stem cell maintenance in vitro and germ cell tumorigenesis in vivo.read more
Citations
More filters
Journal ArticleDOI
Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver
Meritxell Huch,Helmuth Gehart,Ruben van Boxtel,Karien Hamer,Francis Blokzijl,Monique M A Verstegen,Ewa Ellis,Martien van Wenum,Sabine A. Fuchs,Joep de Ligt,Marc van de Wetering,Nobuo Sasaki,Susanne J. Boers,Hans Kemperman,Jeroen de Jonge,Jan N. M. IJzermans,Edward E. S. Nieuwenhuis,Ruurdtje Hoekstra,Stephen C. Strom,Robert R G Vries,Luc J. W. van der Laan,Edwin Cuppen,Hans Clevers +22 more
TL;DR: Conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy.
Journal ArticleDOI
Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
Oluseun Adewumi,Behrouz Aflatoonian,Lars Ährlund-Richter,Michal Amit,Peter W. Andrews,Gemma Beighton,Paul Bello,Nissim Benvenisty,Lorraine S. Berry,Simon Bevan,Barak Blum,Justin Brooking,Kevin G. Chen,Andre Bh Choo,Gary A. Churchill,Marie Corbel,Ivan Damjanov,John S Draper,Petr Dvorak,Petr Dvorak,Katarina Emanuelsson,Roland A. Fleck,Angela Ford,Karin Astrid Maria Gertow,Karin Astrid Maria Gertow,Marina Gertsenstein,Paul J. Gokhale,Rebecca S. Hamilton,Alex Hampl,Alex Hampl,Lyn Healy,Outi Hovatta,Johan Hyllner,Marta P. Imreh,Marta P. Imreh,Joseph Itskovitz-Eldor,Jamie P. Jackson,Jackie Johnson,Mark Jones,Kehkooi Kee,Benjamin L. King,Barbara B. Knowles,Majlinda Lako,Franck Lebrin,Barbara S. Mallon,Daisy Manning,Yoav Mayshar,Ronald D.G. McKay,Anna E. Michalska,Milla Mikkola,Masha Mileikovsky,Stephen L. Minger,Harry Moore,Christine L. Mummery,Andras Nagy,Norio Nakatsuji,Carmel M. O’Brien,Steve Oh,Cia Olsson,Timo Otonkoski,Kye-Yoon Park,Robert Passier,Hema Patel,Minal Patel,Roger A. Pedersen,Martin F. Pera,Marian S Piekarczyk,Renee A. Reijo Pera,Benjamin Reubinoff,Allan J. Robins,Janet Rossant,Peter J. Rugg-Gunn,Peter J. Rugg-Gunn,Thomas C Schulz,Henrik Semb,Eric S Sherrer,Henrike Siemen,Glyn Stacey,Miodrag Stojkovic,Hirofumi Suemori,Jin P. Szatkiewicz,Tikva Turetsky,Timo Tuuri,Steineke van den Brink,Kristina Vintersten,Sanna Vuoristo,Dorien Ward,Thomas A Weaver,Lesley Young,Weidong Zhang +89 more
TL;DR: The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide and found that despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers ofhuman embryonic stem cells.
Journal ArticleDOI
Copy number variation and selection during reprogramming to pluripotency
Samer M.I. Hussein,Nizar N. Batada,Sanna Vuoristo,Reagan W. Ching,Reija Autio,Reija Autio,Elisa Närvä,Siemon Ng,Michel Sourour,Riikka H. Hämäläinen,Cia Olsson,Karolina Lundin,Milla Mikkola,Ras Trokovic,Michael Peitz,Oliver Brüstle,David P. Bazett-Jones,Kari Alitalo,Riitta Lahesmaa,Andras Nagy,Timo Otonkoski +20 more
TL;DR: It is shown that significantly more CNVs are present in early-passage human iPS cells than intermediate passage human i PS cells, fibroblast cell origins and with human embryonic stem (ES) cells.
Journal ArticleDOI
Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture.
Louise C. Laurent,Louise C. Laurent,Igor Ulitsky,Igor Ulitsky,Ileana Slavin,Ha Tran,Andrew J. Schork,Robert Morey,Robert Morey,Candace L. Lynch,Julie V. Harness,Sunray Lee,Maria J. Barrero,Sherman Ku,Marina Martynova,Ruslan Semechkin,Vasiliy Galat,Joel M. Gottesfeld,Juan Carlos Izpisua Belmonte,Charles E. Murry,Hans S. Keirstead,Hyun Sook Park,Uli Schmidt,Andrew L. Laslett,Andrew L. Laslett,Andrew L. Laslett,Franz-Josef Müller,Caroline M. Nievergelt,Ron Shamir,Jeanne F. Loring +29 more
TL;DR: The results illustrate the dynamic nature of genomic abnormalities in pluripotent stem cells and the need for frequent genomic monitoring to assure phenotypic stability and clinical safety.
Journal ArticleDOI
The tumorigenicity of human embryonic and induced pluripotent stem cells
Uri Ben-David,Nissim Benvenisty +1 more
TL;DR: A rapidly accumulating body of evidence suggests that there are important genetic and epigenetic differences between these two cell types, which seem to influence their tumorigenicity.
References
More filters
Journal ArticleDOI
Embryonic Stem Cell Lines Derived from Human Blastocysts
James A. Thomson,Joseph Itskovitz-Eldor,Sander S. Shapiro,Michelle A. Waknitz,Swiergiel Jennifer J,Vivienne S. Marshall,Jeffrey M. Jones +6 more
TL;DR: Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages.
Journal ArticleDOI
Clonally Derived Human Embryonic Stem Cell Lines Maintain Pluripotency and Proliferative Potential for Prolonged Periods of Culture
Michal Amit,Melissa K. Carpenter,Margaret S. Inokuma,Choy-Pik Chiu,Charles P. Harris,Michelle A. Waknitz,Joseph Itskovitz-Eldor,James A. Thomson +7 more
TL;DR: The clonal derivation of two human ES cell lines, H9.1 and H.2, demonstrates the pluripotency of single human ES cells, the maintenance of pluripOTency during an extended period of culture, and the long-term self-renewing properties of cultured human ES Cells.
Journal ArticleDOI
Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines
TL;DR: The results of blastocyst injection studies using three independently isolated XY embryo-derived cell lines, which produce a very high proportion of live-born animals that are overtly chimaeric, are reported.
Journal ArticleDOI
Derivation of human embryonic stem cells in defined conditions.
Tenneille Ludwig,Mark E. Levenstein,Jeffrey M. Jones,Jeffrey M. Jones,W. Travis Berggren,Erika R Mitchen,Jennifer L. Frane,Leann J Crandall,Christine A. Daigh,Kevin R. Conard,Marian S Piekarczyk,Rachel A. Llanas,James A. Thomson +12 more
TL;DR: Feeder-independent human ES cell culture that includes protein components solely derived from recombinant sources or purified from human material is reported.
Journal ArticleDOI
Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells
Jonathan S. Draper,Kath Smith,Paul J. Gokhale,Harry Moore,Edna Maltby,Julie A. Johnson,Lorraine F. Meisner,Thomas P. Zwaka,James A. Thomson,Peter W. Andrews +9 more
TL;DR: It is suggested that increased dosage of chromosome 17q and 12 gene(s) provides a selective advantage for the propagation of undifferentiated hES cells in transplantation therapies in which the use of aneuploid cells could be detrimental.