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Science 6 November 1998:
Vol. 282. no. 5391, pp. 1145 - 1147
DOI: 10.1126/science.282.5391.1145
Prev | Table of Contents

Reports

Embryonic Stem Cell Lines Derived from Human Blastocysts

James A. Thomson, * Joseph Itskovitz-Eldor, Sander S. Shapiro, Michelle A. Waknitz, Jennifer J. Swiergiel, Vivienne S. Marshall, Jeffrey M. Jones

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. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.

J. A. Thomson, M. A. Waknitz, J. J. Swiergiel, V. S. Marshall, Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715, USA. J. Itskovitz-Eldor, Department of Obstetrics and Gynecology, Rambam Medical Center, Faculty of Medicine, Technion, Haifa 31096, Israel. S. S. Shapiro and J. M. Jones, Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI 53715, USA.
*   To whom correspondence should be addressed.

Embryonic stem (ES) cells are derived from totipotent cells of the early mammalian embryo and are capable of unlimited, undifferentiated proliferation in vitro (1, 2). In chimeras with intact embryos, mouse ES cells contribute to a wide range of adult tissues, including germ cells, providing a powerful approach for introducing specific genetic changes into the mouse germ line (3). The term "ES cell" was introduced to distinguish these embryo-derived pluripotent cells from teratocarcinoma-derived pluripotent embryonal carcinoma (EC) cells (2). Given the historical introduction of the term "ES cell" and the properties of mouse ES cells, we proposed that the essential characteristics of primate ES cells should include (i) derivation from the preimplantation or periimplantation embryo, (ii) prolonged undifferentiated proliferation, and (iii) stable developmental potential to form derivatives of all three embryonic germ layers even after prolonged culture (4). For ethical and practical reasons, in many primate species, including humans, the ability of ES cells to contribute to the germ line in chimeras is not a testable property. Nonhuman primate ES cell lines provide an accurate in vitro model for understanding the differentiation of human tissues (4, 5). We now describe human cell lines that fulfill our proposed criteria to define primate ES cells.

Fresh or frozen cleavage stage human embryos, produced by in vitro fertilization (IVF) for clinical purposes, were donated by individuals after informed consent and after institutional review board approval. Embryos were cultured to the blastocyst stage, 14 inner cell masses were isolated, and five ES cell lines originating from five separate embryos were derived, essentially as described for nonhuman primate ES cells (5, 6). The resulting cells had a high ratio of nucleus to cytoplasm, prominent nucleoli, and a colony morphology similar to that of rhesus monkey ES cells (Fig. 1). Three cell lines (H1, H13, and H14) had a normal XY karyotype, and two cell lines (H7 and H9) had a normal XX karyotype. Each of the cell lines was successfully cryopreserved and thawed. Four of the cell lines were cryopreserved after 5 to 6 months of continuous undifferentiated proliferation. The other cell line, H9, retained a normal XX karyotype after 6 months of culture and has now been passaged continuously for more than 8 months (32 passages). A period of replicative crisis was not observed for any of the cell lines.

Fig. 1. Derivation of the H9 cell line. (A) Inner cell mass-derived cells attached to mouse embryonic fibroblast feeder layer after 8 days of culture, 24 hours before first dissociation. Scale bar, 100 µm. (B) H9 colony. Scale bar, 100 µm. (C) H9 cells. Scale bar, 50 µm. (D) Differentiated H9 cells, cultured for 5 days in the absence of mouse embryonic fibroblasts, but in the presence of human LIF (20 ng/ml; Sigma). Scale bar, 100 µm. [View Larger Version of this Image (162K GIF file)]

The human ES cell lines expressed high levels of telomerase activity (Fig. 2). Telomerase is a ribonucleoprotein that adds telomere repeats to chromosome ends and is involved in maintaining telomere length, which plays an important role in replicative life-span (7, 8). Telomerase expression is highly correlated with immortality in human cell lines, and reintroduction of telomerase activity into some diploid human somatic cell lines extends replicative life-span (9). Diploid human somatic cells do not express telomerase, have shortened telomeres with age, and enter replicative senescence after a finite proliferative life-span in tissue culture (10-13). In contrast, telomerase is present at high levels in germ line and embryonic tissues (14). The high level of telomerase activity expressed by the human ES cell lines therefore suggests that their replicative life-span will exceed that of somatic cells.

Fig. 2. Telomerase expression by human ES cell lines. MEF, irradiated mouse embryonic fibroblasts used as a feeder layer for the cells in lanes 4 to 18; 293, adenovirus-transformed kidney epithelial cell line 293; MDA, breast cancer cell line MDA; TSR8, quantitation control template. Telomerase activity was measured with the TRAPEZE Telomerase Detection Kit (Oncor, Gaithersburg, Maryland). The ES cell lines were analyzed at passages 10 to 13. About 2000 cells were assayed for each telomeric repeat amplification protocol assay, and 800 cell equivalents were loaded in each well of a 12.5% nondenaturing polyacrylamide gel. Reactions were done in triplicate with the third sample of each triplet heat inactivated for 10 to 15 min at 85°C before reaction to test for telomerase heat sensitivity (lanes 6, 9, 12, 15, 18, 21, 24, and 27). A 36-base pair internal control for amplification efficiency and quantitative analysis was run for each reaction as indicated by the arrowhead. Data were analyzed with the Storm 840 Scanner and ImageQuant package (Molecular Dynamics). Telomerase activity in the human ES cell lines ranged from 3.8 to 5.9 times that observed in the immortal human cell line MDA on a per cell basis. [View Larger Version of this Image (90K GIF file)]

The human ES cell lines expressed cell surface markers that characterize undifferentiated nonhuman primate ES and human EC cells, including stage-specific embryonic antigen (SSEA)-3, SSEA-4, TRA-l-60, TRA-1-81, and alkaline phosphatase (Fig. 3) (4, 5, 15, 16). The globo-series glycolipid GL7, which carries the SSEA-4 epitope, is formed by the addition of sialic acid to the globo-series glycolipid Gb5, which carries the SSEA-3 epitope (17, 18). Thus, GL7 reacts with antibodies to both SSEA-3 and SSEA-4 (17, 18). Staining intensity for SSEA-4 on the human ES cell lines was consistently strong, but staining intensity for SSEA-3 was weak and varied both within and among colonies (Fig. 3, D and C). Because GL7 carries both the SSEA-4 and SSEA-3 epitopes and because staining for SSEA-4 was consistently strong, the relatively weak staining for SSEA-3 suggests a restricted access of the antibody to the SSEA-3 epitope. In common with human EC cells, the undifferentiated human ES cell lines did not stain for SSEA-1, but differentiated cells stained strongly for SSEA-l (15) (Fig. 3). Mouse inner cell mass cells, ES cells, and EC cells express SSEA-1 but do not express SSEA-3 or SSEA-4 (17, 19), suggesting basic species differences between early mouse and human development.

Fig. 3. Expression of cell surface markers by H9 cells. Scale bar, 100 µm. (A) Alkaline phosphatase. (B) SSEA-1. Undifferentiated cells failed to stain for SSEA- 1 (large colony, left). Occasional colonies consisted of nonstained, central, undifferentiated cells surrounded by a margin of stained, differentiated, epithelial cells (small colony, right). (C) SSEA-3. Some small colonies stained uniformly for SSEA-3 (colony left of center), but most colonies contained a mixture of weakly stained cells and a majority of nonstained cells (colony right of center). (D) SSEA-4. (E) TRA-1-60. (F) TRA-1-81. Similar results were obtained for cell lines H1, H7, H13, and H14. [View Larger Version of this Image (161K GIF file)]

The human ES cell lines were derived by the selection and expansion of individual colonies of a uniform, undifferentiated morphology, but none of the ES cell lines was derived by the clonal expansion of a single cell. The uniform undifferentiated morphology that is shared by human ES and nonhuman primate ES cells and the consistent expression by the human ES cell lines of cell surface markers that uniquely characterize primate ES and human EC cells make it extremely unlikely that a mixed population of precursor cells was expanded. However, because the cell lines were not cloned from a single cell, we cannot rule out the possibility that there is some variation in developmental potential among the undifferentiated cells, in spite of their homogeneous appearance.

The human ES cell lines maintained the potential to form derivatives of all three embryonic germ layers. All five cell lines produced teratomas after injection into severe combined immunodeficient (SCID)-beige mice. Each injected mouse formed a teratoma, and all teratomas included gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm) (Fig. 4). In vitro, the ES cells differentiated when cultured in the absence of mouse embryonic fibroblast feeder layers, both in the presence and absence of human leukemia inhibitory factor (LIF) (Fig. 1). When grown to confluence and allowed to pile up in the culture dish, the ES cell lines differentiated spontaneously even in the presence of fibroblasts. After H9 cells were allowed to differentiate for 2 weeks, both alpha -fetoprotein (350.9 ± 14.2 IU/ml) and human chorionic gonadotropin (hCG, 46.7 ± 5.6 mIU/ml) were detected in conditioned culture medium, indicating endoderm and trophoblast differentiation (20).

Fig. 4. Teratomas formed by the human ES cell lines in SCID-beige mice. Human ES cells after 4 to 5 months of culture (passages 14 to 16) from about 50% confluent six-well plates were injected into the rear leg muscles of 4-week-old male SCID-beige mice (two or more mice per cell line). Seven to eight weeks after injection, the resulting teratomas were examined histologically. (A) Gutlike structures. Cell line H9. Scale bar, 400 µm. (B) Rosettes of neural epithelium. Cell line H14. Scale bar, 200 µm. (C) Bone. Cell line H14. Scale bar, 100 µm. (D) Cartilage. Cell line H9. Scale bar, 100 µm. (E) Striated muscle. Cell line H13. Scale bar, 25 µm. (F) Tubules interspersed with structures resembling fetal glomeruli. Cell line H9. Scale bar, 100 µm. [View Larger Version of this Image (201K GIF file)]

Human ES cells should offer insights into developmental events that cannot be studied directly in the intact human embryo but that have important consequences in clinical areas, including birth defects, infertility, and pregnancy loss. Particularly in the early postimplantation period, knowledge of normal human development is largely restricted to the description of a limited number of sectioned embryos and to analogies drawn from the experimental embryology of other species (21). Although the mouse is the mainstay of experimental mammalian embryology, early structures including the placenta, extraembryonic membranes, and the egg cylinder all differ substantially from the corresponding structure of the human embryo. Human ES cells will be particularly valuable for the study of the development and function of tissues that differ between mice and humans. Screens based on the in vitro differentiation of human ES cells to specific lineages could identify gene targets for new drugs, genes that could be used for tissue regeneration therapies, and teratogenic or toxic compounds.

Elucidating the mechanisms that control differentiation will facilitate the efficient, directed differentiation of ES cells to specific cell types. The standardized production of large, purified populations of euploid human cells such as cardiomyocytes and neurons will provide a potentially limitless source of cells for drug discovery and transplantation therapies. Many diseases, such as Parkinson's disease and juvenile-onset diabetes mellitus, result from the death or dysfunction of just one or a few cell types. The replacement of those cells could offer lifelong treatment. Strategies to prevent immune rejection of the transplanted cells need to be developed but could include banking ES cells with defined major histocompatibility complex backgrounds or genetically manipulating ES cells to reduce or actively combat immune rejection. Because of the similarities to humans and human ES cells, rhesus monkeys and rhesus ES cells provide an accurate model for developing strategies to prevent immune rejection of transplanted cells and for demonstrating the safety and efficacy of ES cell-based therapies. Substantial advances in basic developmental biology are required to direct ES cells efficiently to lineages of human clinical importance. However, progress has already been made in the in vitro differentiation of mouse ES cells to neurons, hematopoietic cells, and cardiac muscle (22-24). Progress in basic developmental biology is now extremely rapid; human ES cells will link this progress even more closely to the prevention and treatment of human disease.

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  27. We thank the personnel of the IVF clinics at the University of Wisconsin School of Medicine and at the Rambam Medical Center for the initial culture and cryopreservation of the embryos used in this study; D. Gardner and M. Lane for the G1.2 and G2.2 media; P. Andrews for the NTERA2 cl.D1 cells and the antibodies used to examine cell surface markers; C. Harris for karyotype analysis; and Geron Corporation for the 293 and MDA cell pellets and for assistance with the telomerase TRAP assay. Supported by the University of Wisconsin (UIR grant 2060) and Geron Corporation (grant 133-BU18).
5 August 1998; accepted 7 October 1998


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An Enhanced Mass Spectrometry Approach Reveals Human Embryonic Stem Cell Growth Factors in Culture.
S. C. Bendall, C. Hughes, J. L. Campbell, M. H. Stewart, P. Pittock, S. Liu, E. Bonneil, P. Thibault, M. Bhatia, and G. A. Lajoie (2009)
Mol. Cell. Proteomics 8, 421-432
   Abstract »    Full Text »    PDF »
ROCK inhibitor improves survival of cryopreserved serum/feeder-free single human embryonic stem cells.
X. Li, R. Krawetz, S. Liu, G. Meng, and D. E. Rancourt (2009)
Hum. Reprod. 24, 580-589
   Abstract »    Full Text »    PDF »
REVIEW PAPER: Cancer Stem Cells and Cancer Nonstem Cells: From Adult Stem Cells or from Reprogramming of Differentiated Somatic Cells.
J. E. Trosko (2009)
Vet. Pathol. 46, 176-193
   Abstract »    Full Text »    PDF »
Integrated Chemical Genomics Reveals Modifiers of Survival in Human Embryonic Stem Cells.
R. Damoiseaux, S. P. Sherman, J. A. Alva, C. Peterson, and A. D. Pyle (2009)
Stem Cells 27, 533-542
   Abstract »    Full Text »    PDF »
Functional Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells.
J. Zhang, G. F. Wilson, A. G. Soerens, C. H. Koonce, J. Yu, S. P. Palecek, J. A. Thomson, and T. J. Kamp (2009)
Circ. Res. 104, e30-e41
   Abstract »    Full Text »    PDF »
Epigenetic reprogramming and induced pluripotency.
K. Hochedlinger and K. Plath (2009)
Development 136, 509-523
   Abstract »    Full Text »    PDF »
Human ESC-derived Neural Rosettes and Neural Stem Cell Progression.
Y. Elkabetz and L. Studer (2009)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Regulation of Pluripotency and Reprogramming by Transcription Factors.
D. Pei (2009)
J. Biol. Chem. 284, 3365-3369
   Abstract »    Full Text »    PDF »
Reviews: Stem Cells and Female Reproduction.
Hongling Du and H. S. Taylor (2009)
Reproductive Sciences 16, 126-139
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Brief Report--Human Embryonic Stem Cell-Derived Mesenchymal Progenitors Possess Strong Immunosuppressive Effects Toward Natural Killer Cells as Well as T Lymphocytes.
B. L. Yen, C. J. Chang, K.-J. Liu, Y. C. Chen, H.-I Hu, C.-H. Bai, and M.-L. Yen (2009)
Stem Cells 27, 451-456
   Abstract »    Full Text »    PDF »
Derivation and Characterization of Canine Embryonic Stem Cell Lines with In Vitro and In Vivo Differentiation Potential.
A. K. Vaags, S. Rosic-Kablar, C. J. Gartley, Y. Z. Zheng, A. Chesney, D. A.F. Villagomez, S. A. Kruth, and M. R. Hough (2009)
Stem Cells 27, 329-340
   Abstract »    Full Text »    PDF »
Genetic Analysis of the Role of the Reprogramming Gene LIN-28 in Human Embryonic Stem Cells.
H. Darr and N. Benvenisty (2009)
Stem Cells 27, 352-362
   Abstract »    Full Text »    PDF »
Markers that define stemness in ESC are unable to identify the totipotent cells in human preimplantation embryos.
G. Cauffman, M. De Rycke, K. Sermon, I. Liebaers, and H. Van de Velde (2009)
Hum. Reprod. 24, 63-70
   Abstract »    Full Text »    PDF »
A Feeder-Free and Efficient Production of Functional Neutrophils from Human Embryonic Stem Cells.
K. Saeki, K. Saeki, M. Nakahara, S. Matsuyama, N. Nakamura, Y. Yogiashi, A. Yoneda, M. Koyanagi, Y. Kondo, and A. Yuo (2009)
Stem Cells 27, 59-67
   Abstract »    Full Text »    PDF »
A Novel Approach for the Derivation of Putative Primordial Germ Cells and Sertoli Cells from Human Embryonic Stem Cells.
N. Bucay, M. Yebra, V. Cirulli, I. Afrikanova, T. Kaido, A. Hayek, and A. M.P. Montgomery (2009)
Stem Cells 27, 68-77
   Abstract »    Full Text »    PDF »
Human Embryonic Stem Cell Differentiation Toward Regional Specific Neural Precursors.
S. Erceg, M. Ronaghi, and M. Stojkovic (2009)
Stem Cells 27, 78-87
   Abstract »    Full Text »    PDF »
Isolation and Characterization of Pluripotent Human Spermatogonial Stem Cell-Derived Cells.
N. Kossack, J. Meneses, S. Shefi, H. N. Nguyen, S. Chavez, C. Nicholas, J. Gromoll, P. J. Turek, and R. A. Reijo-Pera (2009)
Stem Cells 27, 138-149
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In vivo commitment and functional tissue regeneration using human embryonic stem cell-derived mesenchymal cells.
N. S. Hwang, S. Varghese, H. J. Lee, Z. Zhang, Z. Ye, J. Bae, L. Cheng, and J. Elisseeff (2008)
PNAS 105, 20641-20646
   Abstract »    Full Text »    PDF »
Dissecting Signaling Pathways That Govern Self-renewal of Rabbit Embryonic Stem Cells.
S. Wang, Y. Shen, X. Yuan, K. Chen, X. Guo, Y. Chen, Y. Niu, J. Li, R.-H. Xu, X. Yan, et al. (2008)
J. Biol. Chem. 283, 35929-35940
   Abstract »    Full Text »    PDF »
Esrrb Activates Oct4 Transcription and Sustains Self-renewal and Pluripotency in Embryonic Stem Cells.
X. Zhang, J. Zhang, T. Wang, M. A. Esteban, and D. Pei (2008)
J. Biol. Chem. 283, 35825-35833
   Abstract »    Full Text »    PDF »
The ethics of stem cell research: can the disagreements be resolved?.
J. H. Solbakk and S. Holm (2008)
J. Med. Ethics 34, 831-832
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What happened to the stem cells?.
T Hviid Nielsen (2008)
J. Med. Ethics 34, 852-857
   Abstract »    Full Text »    PDF »
Novel cryopreservation method for dissociated human embryonic stem cells in the presence of a ROCK inhibitor.
R. Martin-Ibanez, C. Unger, A. Stromberg, D. Baker, J.M. Canals, and O. Hovatta (2008)
Hum. Reprod. 23, 2744-2754
   Abstract »    Full Text »    PDF »
OCT4 Spliced Variants Are Differentially Expressed in Human Pluripotent and Nonpluripotent Cells.
Y. Atlasi, S. J. Mowla, S. A.M. Ziaee, P. J. Gokhale, and P. W. Andrews (2008)
Stem Cells 26, 3068-3074
   Abstract »    Full Text »    PDF »
Secreted Proteoglycans Directly Mediate Human Embryonic Stem Cell-Basic Fibroblast Growth Factor 2 Interactions Critical for Proliferation.
M. E. Levenstein, W. T. Berggren, J. E. Lee, K. R. Conard, R. A. Llanas, R. J. Wagner, L. M. Smith, and J. A. Thomson (2008)
Stem Cells 26, 3099-3107
   Abstract »    Full Text »    PDF »
Mouse Meningiocytes Express Sox2 and Yield High Efficiency of Chimeras after Nuclear Reprogramming with Exogenous Factors.
D. Qin, Y. Gan, K. Shao, H. Wang, W. Li, T. Wang, W. He, J. Xu, Y. Zhang, Z. Kou, et al. (2008)
J. Biol. Chem. 283, 33730-33735
   Abstract »    Full Text »    PDF »
Generation of Cardiomyocytes from New Human Embryonic Stem Cell Lines Derived from Poor-quality Blastocysts.
A. Raya, I. Rodriguez-Piza, B. Aran, A. Consiglio, P.N. Barri, A. Veiga, and J.C. Izpisua Belmonte (2008)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Cardiogenic Differentiation and Transdifferentiation of Progenitor Cells.
H. Reinecke, E. Minami, W.-Z. Zhu, and M. A. Laflamme (2008)
Circ. Res. 103, 1058-1071
   Abstract »    Full Text »    PDF »
Ronin and Caspases in Embryonic Stem Cells: A New Perspective on Regulation of the Pluripotent State.
T.P. Zwaka (2008)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
On Women, Egg Cells and Embryos: Gender in the Regulatory Debates on Embryonic Research in the Netherlands.
M. Kirejczyk (2008)
European Journal of Women's Studies 15, 377-391
   Abstract »    PDF »
Assisted reproductive technologies are an integrated part of national strategies addressing demographic and reproductive challenges.
S. Ziebe, P. Devroey, and on behalf of the State of the ART 2007 Workshop Gr (2008)
Hum. Reprod. Update 14, 583-592
   Abstract »    Full Text »    PDF »
Chemically defined sequential culture media for TH+ cell derivation from human embryonic stem cells.
T. Song, G. Chen, Y. Wang, G. Mao, Y. Wang, and H. Bai (2008)
Mol. Hum. Reprod. 14, 619-625
   Abstract »    Full Text »    PDF »
Rho-associated kinase inhibitor Y-27632 promotes survival of cynomolgus monkey embryonic stem cells.
T. Takehara, T. Teramura, Y. Onodera, R. Kakegawa, N. Fukunaga, M. Takenoshita, N. Sagawa, K. Fukuda, and Y. Hosoi (2008)
Mol. Hum. Reprod. 14, 627-634
   Abstract »    Full Text »    PDF »
Feeder-Free Monolayer Cultures of Human Embryonic Stem Cells Express an Epithelial Plasma Membrane Protein Profile.
D. Van Hoof, S. R. Braam, W. Dormeyer, D. Ward-van Oostwaard, A. J.R. Heck, J. Krijgsveld, and C. L. Mummery (2008)
Stem Cells 26, 2777-2781
   Abstract »    Full Text »    PDF »
Enrichment and Differentiation of Human Germ-Like Cells Mediated by Feeder Cells and Basic Fibroblast Growth Factor Signaling.
F. D. West, D. W. Machacek, N. L. Boyd, K. Pandiyan, K. R. Robbins, and S. L. Stice (2008)
Stem Cells 26, 2768-2776
   Abstract »    Full Text »    PDF »
Expression of angiotensin-converting enzyme (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells.
E. T. Zambidis, T. Soon Park, W. Yu, A. Tam, M. Levine, X. Yuan, M. Pryzhkova, and B. Peault (2008)
Blood 112, 3601-3614
   Abstract »    Full Text »    PDF »
Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state.
S.-L. Lin, D. C. Chang, S. Chang-Lin, C.-H. Lin, D. T.S. Wu, D. T. Chen, and S.-Y. Ying (2008)
RNA 14, 2115-2124
   Abstract »    Full Text »    PDF »
Expression profiles of protein tyrosine kinase genes in human embryonic stem cells.
M.-Y. Son, J. Kim, H.-W. Han, S.-M. Woo, Y. S. Cho, Y.-K. Kang, and Y.-M. Han (2008)
Reproduction 136, 423-432
   Abstract »    Full Text »    PDF »
Similar biological characteristics of human embryonic stem cell lines with normal and abnormal karyotypes.
X. Sun, X. Long, Y. Yin, Y. Jiang, X. Chen, W. Liu, W. Zhang, H. Du, S. Li, Y. Zheng, et al. (2008)
Hum. Reprod. 23, 2185-2193
   Abstract »    Full Text »    PDF »
Glycan stem-cell markers are specifically expressed by spermatogonia in the adult non-human primate testis.
T. Muller, K. Eildermann, R. Dhir, S. Schlatt, and R. Behr (2008)
Hum. Reprod. 23, 2292-2298
   Abstract »    Full Text »    PDF »
Lentiviral-Mediated HoxB4 Expression in Human Embryonic Stem Cells Initiates Early Hematopoiesis in a Dose-Dependent Manner but Does Not Promote Myeloid Differentiation.
C. Unger, E. Karner, A. Treschow, B. Stellan, U. Felldin, H. Concha, M. Wendel, O. Hovatta, A. Aints, L. Ahrlund-Richter, et al. (2008)
Stem Cells 26, 2455-2466
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OP9 Stroma Augments Survival of Hematopoietic Precursors and Progenitors During Hematopoietic Differentiation from Human Embryonic Stem Cells.
J. Ji, K. Vijayaragavan, M. Bosse, K. Weisel, and M. Bhatia (2008)
Stem Cells 26, 2485-2495
   Abstract »    Full Text »    PDF »
CD34+ Testicular Stromal Cells Support Long-Term Expansion of Embryonic and Adult Stem and Progenitor Cells.
J. Kim, M. Seandel, I. Falciatori, D. Wen, and S. Rafii (2008)
Stem Cells 26, 2516-2522
   Abstract »    Full Text »    PDF »
Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood-derived hematopoietic progenitor cells.
C. H. Martin, P. S. Woll, Z. Ni, J. C. Zuniga-Pflucker, and D. S. Kaufman (2008)
Blood 112, 2730-2737
   Abstract »    Full Text »    PDF »
Highly efficient transient gene expression and gene targeting in primate embryonic stem cells with helper-dependent adenoviral vectors.
K. Suzuki, K. Mitsui, E. Aizawa, K. Hasegawa, E. Kawase, T. Yamagishi, Y. Shimizu, H. Suemori, N. Nakatsuji, and K. Mitani (2008)
PNAS 105, 13781-13786
   Abstract »    Full Text »    PDF »
Heparin promotes the growth of human embryonic stem cells in a defined serum-free medium.
M. K. Furue, J. Na, J. P. Jackson, T. Okamoto, M. Jones, D. Baker, R.-I. Hata, H. D. Moore, J. D. Sato, and P. W. Andrews (2008)
PNAS 105, 13409-13414
   Abstract »    Full Text »    PDF »
Combinatorial Signals of Activin/Nodal and Bone Morphogenic Protein Regulate the Early Lineage Segregation of Human Embryonic Stem Cells.
Z. Wu, W. Zhang, G. Chen, L. Cheng, J. Liao, N. Jia, Y. Gao, H. Dai, J. Yuan, L. Cheng, et al. (2008)
J. Biol. Chem. 283, 24991-25002
   Abstract »    Full Text »    PDF »
Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts.
R.-J. Swijnenburg, S. Schrepfer, J. A. Govaert, F. Cao, K. Ransohoff, A. Y. Sheikh, M. Haddad, A. J. Connolly, M. M. Davis, R. C. Robbins, et al. (2008)
PNAS 105, 12991-12996
   Abstract »    Full Text »    PDF »
Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis.
F. Ma, Y. Ebihara, K. Umeda, H. Sakai, S. Hanada, H. Zhang, Y. Zaike, E. Tsuchida, T. Nakahata, H. Nakauchi, et al. (2008)
PNAS 105, 13087-13092
   Abstract »    Full Text »    PDF »
Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cells Express the Serotonin Receptor and Are Susceptible to JC Virus Infection.
C. Schaumburg, B. A. O'Hara, T. E. Lane, and W. J. Atwood (2008)
J. Virol. 82, 8896-8899
   Abstract »    Full Text »    PDF »
Prevention of Amino Acid Conversion in SILAC Experiments with Embryonic Stem Cells.
S. C. Bendall, C. Hughes, M. H. Stewart, B. Doble, M. Bhatia, and G. A. Lajoie (2008)
Mol. Cell. Proteomics 7, 1587-1597
   Abstract »    Full Text »    PDF »
In Search of the In Vivo Identity of Mesenchymal Stem Cells.
L. da Silva Meirelles, A. I. Caplan, and N. B. Nardi (2008)
Stem Cells 26, 2287-2299
   Abstract »    Full Text »    PDF »
Control of Human Embryonic Stem Cell Colony and Aggregate Size Heterogeneity Influences Differentiation Trajectories.
C. L. Bauwens, R. Peerani, S. Niebruegge, K. A. Woodhouse, E. Kumacheva, M. Husain, and P. W. Zandstra (2008)
Stem Cells 26, 2300-2310
   Abstract »    Full Text »    PDF »
Recombinant Vitronectin Is a Functionally Defined Substrate That Supports Human Embryonic Stem Cell Self-Renewal via {alpha}V{beta}5 Integrin.
S. R. Braam, L. Zeinstra, S. Litjens, D. Ward-van Oostwaard, S. van den Brink, L. van Laake, F. Lebrin, P. Kats, R. Hochstenbach, R. Passier, et al. (2008)
Stem Cells 26, 2257-2265
   Abstract »    Full Text »    PDF »
Stem Cell-Derived Therapeutic Myelin Repair Requires 7% Cell Replacement.
M. E. Kiel, C. P. Chen, D. Sadowski, and R. D. McKinnon (2008)
Stem Cells 26, 2229-2236
   Abstract »    Full Text »    PDF »
Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons.
J. T. Dimos, K. T. Rodolfa, K. K. Niakan, L. M. Weisenthal, H. Mitsumoto, W. Chung, G. F. Croft, G. Saphier, R. Leibel, R. Goland, et al. (2008)
Science 321, 1218-1221
   Abstract »    Full Text »    PDF »
Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling.
D. C. Hay, J. Fletcher, C. Payne, J. D. Terrace, R. C. J. Gallagher, J. Snoeys, J. R. Black, D. Wojtacha, K. Samuel, Z. Hannoun, et al. (2008)
PNAS 105, 12301-12306
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)