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Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: Vol. 7; Issue 19; 20 September 2005 Abstract
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Summary of differentiation schemes used to produce various cell types from human embryonic stem cells
Louise A. Hyslop, Lyle Armstrong, Miodrag Stojkovic and Majlinda Lako
| Table 3. Summary of differentiation schemes used to produce various cell types from human embryonic stem cells | |||
| Cell derivative | Method outline | Comment | Refs |
| Ectoderm | |||
|
Keratinocytes |
EBs plated on monolayer | Progressive succession of keratinocyte markers | 117 |
| Neuronal
cells
|
EBs in medium supplemented with GFs | RA and NGF enhanced neuronal differentiation | 118 |
| Neurospheres in medium with FGF-2 and EGF | Neural progenitors were maintained in culture up to 20 weeks | 119 | |
|
EBs plated, and medium supplemented with FGF-2 |
Neural precursors differentiated into neurons, astrocytes and oligodendrocytes | 120 | |
|
EBs in medium conditioned by HepG2 cells |
Differentiation into neurons expressing MAP-2, neurofilament H or TH markers | 121 | |
|
hESCs seeded on scaffold, and medium supplemented with GFs |
Neural rosette-like structures developed throughout the scaffolds | 122 | |
|
Co-culture of hESCs with PA6 stromal cells |
Neural cells co-expressed markers of sympathetic and peripheral sensory neurons | 123 | |
|
Dopaminergic neurons |
Co-culture of hESCs with PA6 stromal cells | Dopaminergic neurons integrated into rat striatum | 124 |
|
Co-culture of hESCs with PA6 cells; then culture on fibronectin-coated plates in medium with GFs |
95% of differentiated cells expressed neural precursor markers and >40% were TH+ | 125 | |
|
Co-culture of hESCs with Ms5 or S2 cells; replated in medium with GFs |
High yield of dopaminergic neurons | 60 | |
| Mesoderm | |||
|
Cardiomyocytes |
Spontaneous differentiation of hESCs |
Culture and differentiation enhanced with 5-aza-2'-deoxycytidine |
70 |
|
EBs plated on gelatine-coated plates; contracting areas were dissected |
Formed structural and electromechanical connections with cultured rat cardiomyocytes | 56, 69 | |
|
Co-culture of hESCs with visceral- endoderm-like cells |
Cardiomyocytes were immature | 57 | |
|
Endothelial cells |
EBs plated on Matrigel-coated plates in endothelial medium |
Isolated PECAM1+ cells displayed characteristics similar to vessel endothelium |
126 |
| Haematopoietic precursors |
hESCs encapsulated in agarose hydrogel microcapsules and stirred in bioreactors |
Enhanced differentiation of progenitors especially under hypoxic conditions | 127 |
|
EBs in medium containing serum and/or cytokines |
Progenitors restricted to progeny population expressing cell surface CD45 | 58 | |
|
Co-culture of hESCs with S17 or C166 stromal cells |
Myeloid, erythroid and megakaryocytic differentiation observed | 59, 128 | |
|
Co-culture of hESCs with OP9 stromal cells |
CD34+ cells generated could differentiate to myeloid and lymphoid cells | 129 | |
| Osteogenic cells | hESCs treated with osteogenic factors | Mineralised nodules composed of hydroxyapatite were established in culture | 130 |
| Endoderm | |||
|
Hepatocytes |
hESCs treated with sodium butyrate |
Differentiated cells showed morphological features of primary hepatocytes, and expressed liver-associated proteins |
131 |
|
hESCs on collagen-I-coated plates in modified medium |
Differentiated cells expressed human albumin | 132 | |
|
Nonfunctional insulin-secreting cells |
EB differentiation in medium supplemented with FGF-2 |
Occasional insulin-expressing cells in day 14 EBs, with increase in number by day 19 |
133 |
| Extraembryonic tissues | |||
|
Extraembryonic endoderm |
hESCs treated with BMP-2 |
BMP-2 controls differentiation to extraembryonic endoderm |
134 |
| Trophectoderm |
hESCs treated with BMP-4 in serum-free medium containing FGF-2 |
Range of trophoblast markers expressed and placental hormones secreted | 28 |
| Germ cells | |||
|
Germ cells |
Spontaneous differentiation using the EB system |
Immature and mature germ cell markers expressed during EB differentiation |
135 |
| Abbreviations: BMP, bone morphogenetic protein; EBs, embryoid bodies; EGF, epidermal growth factor; FGF-2, basic fibroblast growth factor; GFs, growth factors; hESCs, human embryonic stem cells; MAP-2, microtubule associated protein 2; NGF, nerve growth factor; RA, retinoic acid; TH, tyrosine hydroxylase; PECAM1, platelet endothelial cell adhesion molecule 1. | |||
| References cited
in Table 3
28 Xu, R.H. et al. (2002) BMP4 initiates human embryonic stem cell differentiation to trophoblast. Nat Biotechnol 20, 1261-1264, PubMed 56 Kehat, I. et al. (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 108, 407-414, PubMed 57 Mummery, C. et al. (2002) Cardiomyocyte differentiation of mouse and human embryonic stem cells. J Anat 200, 233-242, PubMed 58 Chadwick, K. et al. (2003) Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells. Blood 102, 906-915, PubMed 59 Tian, X. et al. (2004) Cytokine requirements differ for stroma and embryoid body-mediated hematopoiesis from human embryonic stem cells. Exp Hematol 32, 1000-1009, PubMed 60 Perrier, A.L. et al. (2004) Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci U S A 101, 12543-12548, PubMed 69 Kehat, I. et al. (2004) Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol 22, 1282-1289, PubMed 70 Xu, C. et al. (2002) Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res 91, 501-508, PubMed 117 Green, H., Easley, K. and Iuchi, S. (2003) Marker succession during the development of keratinocytes from cultured human embryonic stem cells. Proc Natl Acad Sci U S A 100, 15625-15630, PubMed 118 Schuldiner, M. et al. (2001) Induced neuronal differentiation of human embryonic stem cells. Brain Res 913, 201-205, PubMed 119 Reubinoff, B.E. et al. (2001) Neural progenitors from human embryonic stem cells. Nat Biotechnol 19, 1134-1140, PubMed 120 Zhang, S.C. et al. (2001) In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol 19, 1129-1133, PubMed 121 Schulz, T.C. et al. (2003) Directed neuronal differentiation of human embryonic stem cells. BMC Neurosci 4, 27, PubMed 122 Levenberg, S. et al. (2005) Neurotrophin-induced differentiation of human embryonic stem cells on three-dimensional polymeric scaffolds. Tissue Eng 11, 506-512, PubMed 123 Pomp, O. et al. (2005) Generation of peripheral sensory and sympathetic neurons and neural crest cells from human embryonic stem cells. Stem Cells 23, 923-990, PubMed 124 Zeng, X. et al. (2004) Dopaminergic differentiation of human embryonic stem cells. Stem Cells 22, 925-940, PubMed 125 Park, C.H. et al. (2005) In vitro and in vivo analyses of human embryonic stem cell-derived dopamine neurons. J Neurochem 92, 1265-1276, PubMed 126 Levenberg, S. et al. (2002) Endothelial cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A 99, 4391-4396, PubMed 127 Dang, S.M. et al. (2002) Efficiency of embryoid body formation and hematopoietic development from embryonic stem cells in different culture systems. Biotechnol Bioeng 78, 442-453, PubMed 128 Kaufman, D.S. et al. (2001) Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A 98, 10716-10721, PubMed 129 Vodyanik, M.A. et al. (2005) Human embryonic stem cell-derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential. Blood 105, 617-626, PubMed 130 Sottile, V., Thomson, A. and McWhir, J. (2003) In vitro osteogenic differentiation of human ES cells. Cloning Stem Cells 5, 149-155, PubMed 131 Rambhatla, L. et al. (2003) Generation of hepatocyte-like cells from human embryonic stem cells. Cell Transplant 12, 1-11, PubMed 132 Shirahashi, H. et al. (2004) Differentiation of human and mouse embryonic stem cells along a hepatocyte lineage. Cell Transplant 13, 197-211, PubMed 133 Assady, S. et al. (2001) Insulin production by human embryonic stem cells. Diabetes 50, 1691-1697, PubMed 134 Pera, M.F. et al. (2004) Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist noggin. J Cell Sci 117, 1269-1280, PubMed 135 Clark, A.T. et al. (2004) Spontaneous differentiation of germ cells from human embryonic stem cells in vitro. Hum Mol Genet 13, 727-739, PubMed |
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