Bioengineering embryonic stem cell microenvironments for the study of breast cancer

International Journal of Molecular Sciences

Volumn 12, Issue 11, 2011, Pages 7662-7691

  Raof, Nurazhani Abdul ^a   Mooney, Bridget M ^a   Xie, Yubing ^a  

^a STATE UNIVERSITY OF NEW YORK   (United States)

Author keywords

Breast cancer; Co culture; Hydrogel; Metastasis; Microenvironment; Stem cell; Three dimensional culture

Indexed keywords

TISSUE INHIBITOR OF METALLOPROTEINASE 1; TISSUE INHIBITOR OF METALLOPROTEINASE 2; TRANSFORMING GROWTH FACTOR BETA; TRASTUZUMAB; WNT PROTEIN;

BIOENGINEERING; BREAST CANCER; BREAST CARCINOGENESIS; CANCER INHIBITION; CANCER INVASION; CANCER STEM CELL; CELL DIFFERENTIATION; CELL INTERACTION; CELL PROLIFERATION; EMBRYOLOGY; EMBRYONIC MICROENVIRONMENT; EMBRYONIC STEM CELL; EPITHELIAL MESENCHYMAL TRANSITION; EXTRACELLULAR MATRIX; HUMAN; METASTASIS INHIBITION; MIGRATION INHIBITION; NONHUMAN; ONCOGENE; PLURIPOTENT STEM CELL; REVIEW; TUMOR GROWTH; TUMOR MICROENVIRONMENT; TUMOR SUPPRESSOR GENE; ANIMAL; BREAST NEOPLASMS; DISEASE MODEL; FEMALE; METABOLISM; PROCEDURES; STEM CELL NICHE;

ANIMALS; BIOENGINEERING; BREAST NEOPLASMS; DISEASE MODELS, ANIMAL; EMBRYONIC STEM CELLS; FEMALE; HUMANS; STEM CELL NICHE; TUMOR MICROENVIRONMENT;

EID: 82255164575     PISSN: None     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms12117662     Document Type: Review

References (189)

1. Siegel, R.; Ward, E.; Brawley, O.; Jemal, A. Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J. Clin. 2011, 61, 212-236.
2. Gluck, S. The prevention and management of distant metastases in women with breast cancer. Cancer Invest. 2007, 25, 6-13.
3. Mehlen, P.; Puisieux, A. Metastasis: A question of life or death. Nat. Rev. Cancer 2006, 6, 449-458.
4. Finger, E.C.; Giaccia, A.J. Hypoxia, inflammation, and the tumor microenvironment in metastatic disease. Cancer Metastasis Rev. 2010, 29, 285-293.
5. Chaffer, C.L.; Weinberg, R.A. A perspective on cancer cell metastasis. Science 2011, 331, 1559-1564.
6. Bissell, M.J.; Labarge, M.A. Context, tissue plasticity, and cancer: Are tumor stem cells also regulated by the microenvironment? Cancer Cell 2005, 7, 17-23.
7. Weigelt, B.; Bissell, M.J. Unraveling the microenvironmental influences on the normal mammary gland and breast cancer. Semin. Cancer Biol. 2008, 18, 311-321.
8. Ma, X.J.; Dahiya, S.; Richardson, E.; Erlander, M.; Sgroi, D.C. Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Res. 2009, 11, R7:1-R7:18.
9. Carlini, M.J.; de Lorenzo, M.S.; Puricelli, L. Cross-talk between tumor cells and the microenvironment at the metastatic niche. Curr. Pharm. Biotechnol. 2011, in press.
10. Croci, D.; Salatino, M. Tumor immune escape mechanisms that operate during metastasis. Curr. Pharm. Biotechnol. 2011, in press.
11. Joyce, J.A.; Pollard, J.W. Microenvironmental regulation of metastasis. Nat. Rev. Cancer 2009, 9, 239-252.
12. Barbolina, M.V.; Moss, N.M.; Westfall, S.D.; Liu, Y.; Burkhalter, R.J.; Marga, F.; Forgacs, G.; Hudson, L.G.; Stack, M.S. Microenvironmental regulation of ovarian cancer metastasis. Cancer Treat. Res. 2009, 149, 319-334.
13. Lathia, J.D.; Heddleston, J.M.; Venere, M.; Rich, J.N. Deadly teamwork: Neural cancer stem cells and the tumor microenvironment. Cell Stem Cell 2011, 8, 482-485.
14. Jagannathan, N.R.; Bhujwalla, Z.M. Tumor microenvironment in cancer treatment and metastasis. NMR Biomed. 2011, 24, 559-560.
15. Cichon, M.A.; Degnim, A.C.; Visscher, D.W.; Radisky, D.C. Microenvironmental influences that drive progression from benign breast disease to invasive breast cancer. J. Mammary Gland Biol. Neoplasia 2010, 15, 389-397.
16. Malchenko, S.; Galat, V.; Seftor, E.A.; Vanin, E.F.; Costa, F.F.; Seftor, R.E.; Soares, M.B.; Hendrix, M.J. Cancer hallmarks in induced pluripotent cells: New insights. J. Cell. Physiol. 2010, 225, 390-393.
17. Topczewska, J.M.; Postovit, L.M.; Margaryan, N.V.; Sam, A.; Hess, A.R.; Wheaton, W.W.; Nickoloff, B.J.; Topczewski, J.; Hendrix, M.J. Embryonic and tumorigenic pathways converge via nodal signaling: Role in melanoma aggressiveness. Nat. Med. 2006, 12, 925-932.
18. Abbott, D.E.; Postovit, L.M.; Seftor, E.A.; Margaryan, N.V.; Seftor, R.E.; Hendrix, M.J. Exploiting the convergence of embryonic and tumorigenic signaling pathways to develop new therapeutic targets. Stem Cell Rev. 2007, 3, 68-78.
19. Postovit, L.M.; Costa, F.F.; Bischof, J.M.; Seftor, E.A.; Wen, B.; Seftor, R.E.; Feinberg, A.P.; Soares, M.B.; Hendrix, M.J. The commonality of plasticity underlying multipotent tumor cells and embryonic stem cells. J. Cell. Biochem. 2007, 101, 908-917.
20. Ingber, D.E. Can cancer be reversed by engineering the tumor microenvironment? Semin. Cancer Biol. 2008, 18, 356-364.
21. Giuffrida, D.; Rogers, I.M.; Nagy, A.; Calogero, A.E.; Brown, T.J.; Casper, R.F. Human embryonic stem cells secrete soluble factors that inhibit cancer cell growth. Cell Prolif. 2009, 42, 788-798.
22. Costa, F.F.; Seftor, E.A.; Bischof, J.M.; Kirschmann, D.A.; Strizzi, L.; Arndt, K.; de Fatima Bonaldo, M.; Soares, M.B.; Hendrix, M.J. Epigenetically reprogramming metastatic tumor cells with an embryonic microenvironment. Epigenomics 2009, 1, 387-398.
23. Postovit, L.M.; Margaryan, N.V.; Seftor, E.A.; Kirschmann, D.A.; Lipavsky, A.; Wheaton, W.W.; Abbott, D.E.; Seftor, R.E.; Hendrix, M.J. Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells. Proc. Natl. Acad. Sci. USA 2008, 105, 4329-4334.
24. Kulesa, P.M.; Kasemeier-Kulesa, J.C.; Teddy, J.M.; Margaryan, N.V.; Seftor, E.A.; Seftor, R.E.; Hendrix, M.J. Reprogramming metastatic melanoma cells to assume a neural crest cell-like phenotype in an embryonic microenvironment. Proc. Natl. Acad. Sci. USA 2006, 103, 3752-3757.
25. Kim, M.O.; Kim, S.H.; Oi, N.; Lee, M.H.; Yu, D.H.; Kim, D.J.; Cho, E.J.; Bode, A.M.; Cho, Y.Y.; Bowden, T.G., et al. Embryonic stem-cell-preconditioned microenvironment induces loss of cancer cell properties in human melanoma cells. Pigment Cell Melanoma Res. 2011, 24, 922-931.
26. Tzukerman, M.; Rosenberg, T.; Reiter, I.; Ben-Eliezer, S.; Denkberg, G.; Coleman, R.; Reiter, Y.; Skorecki, K. The influence of a human embryonic stem cell-derived microenvironment on targeting of human solid tumor xenografts. Cancer Res. 2006, 66, 3792-3801.
27. Wang, Z.; Zhang, L.; Yeung, T.K.; Chen, X. Endocytosis deficiency of epidermal growth factor (egf) receptor-erbb2 heterodimers in response to egf stimulation. Mol. Biol. Cell 1999, 10, 1621-1636.
28. Caldon, C.E.; Sutherland, R.L.; Musgrove, E. Cell cycle proteins in epithelial cell differentiation: Implications for breast cancer. Cell Cycle 2010, 9, 1918-1928.
29. Lee, E.Y.; Muller, W.J. Oncogenes and tumor suppressor genes. Cold Spring Harb. Perspect. Biol. 2010, 2, a003236.
30. Hollestelle, A.; Nagel, J.H.; Smid, M.; Lam, S.; Elstrodt, F.; Wasielewski, M.; Ng, S.S.; French, P.J.; Peeters, J.K.; Rozendaal, M.J., et al. Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines. Breast Cancer Res. Treat. 2010, 121, 53-64.
31. Mackay, A.; Tamber, N.; Fenwick, K.; Iravani, M.; Grigoriadis, A.; Dexter, T.; Lord, C.J.; Reis-Filho, J.S.; Ashworth, A. A high-resolution integrated analysis of genetic and expression profiles of breast cancer cell lines. Breast Cancer Res. Treat. 2009, 118, 481-498.
32. Kao, J.; Salari, K.; Bocanegra, M.; Choi, Y.L.; Girard, L.; Gandhi, J.; Kwei, K.A.; Hernandez-Boussard, T.; Wang, P.; Gazdar, A.F., et al. Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery. PLoS One 2009, 4, e6146:1-e6146:16.
33. Kessenbrock, K.; Plaks, V.; Werb, Z. Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell 2010, 141, 52-67.
34. Herrera-Gayol, A.; Jothy, S. Adhesion proteins in the biology of breast cancer: Contribution of cd44. Exp. Mol. Pathol. 1999, 66, 149-156.
35. Sethi, S.; Sarkar, F.H.; Ahmed, Q.; Bandyopadhyay, S.; Nahleh, Z.A.; Semaan, A.; Sakr, W.; Munkarah, A.; Ali-Fehmi, R. Molecular markers of epithelial-to-mesenchymal transition are associated with tumor aggressiveness in breast carcinoma. Transl. Oncol. 2011, 4, 222-226.
36. Taherian, A.; Li, X.; Liu, Y.; Haas, T.A. Differences in integrin expression and signaling within human breast cancer cells. BMC Cancer 2011, 11, 293:1-293:15.
37. Creighton, C.J.; Chang, J.C.; Rosen, J.M. Epithelial-mesenchymal transition (emt) in tumor-initiating cells and its clinical implications in breast cancer. J. Mammary Gland Biol. Neoplasia 2010, 15, 253-260.
38. Micalizzi, D.S.; Farabaugh, S.M.; Ford, H.L. Epithelial-mesenchymal transition in cancer: Parallels between normal development and tumor progression. J. Mammary Gland Biol. Neoplasia 2010, 15, 117-134.
39. Chen, J.; Yao, Y.; Gong, C.; Yu, F.; Su, S.; Liu, B.; Deng, H.; Wang, F.; Lin, L.; Yao, H., et al. Ccl18 from tumor-associated macrophages promotes breast cancer metastasis via pitpnm3. Cancer Cell 2011, 19, 541-555.
40. Li, J.Y.; Ou, Z.L.; Yu, S.J.; Gu, X.L.; Yang, C.; Chen, A.X.; Di, G.H.; Shen, Z.Z.; Shao, Z.M. The chemokine receptor ccr4 promotes tumor growth and lung metastasis in breast cancer. Breast Cancer Res. Treat. 2011, in press.
41. Johnson-Holiday, C.; Singh, R.; Johnson, E.; Singh, S.; Stockard, C.R.; Grizzle, W.E.; Lillard, J.W., Jr. Ccl25 mediates migration, invasion and matrix metalloproteinase expression by breast cancer cells in a ccr9-dependent fashion. Int. J. Oncol. 2011, 38, 1279-1285.
42. Allinen, M.; Beroukhim, R.; Cai, L.; Brennan, C.; Lahti-Domenici, J.; Huang, H.; Porter, D.; Hu, M.; Chin, L.; Richardson, A., et al. Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell 2004, 6, 17-32.
43. Patsialou, A.; Wyckoff, J.; Wang, Y.; Goswami, S.; Stanley, E.R.; Condeelis, J.S. Invasion of human breast cancer cells in vivo requires both paracrine and autocrine loops involving the colony-stimulating factor-1 receptor. Cancer Res. 2009, 69, 9498-9506.
44. Sarrio, D.; Rodriguez-Pinilla, S.M.; Hardisson, D.; Cano, A.; Moreno-Bueno, G.; Palacios, J. Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res. 2008, 68, 989-997.
45. Takebe, N.; Warren, R.Q.; Ivy, S.P. Breast cancer growth and metastasis: Interplay between cancer stem cells, embryonic signaling pathways and epithelial-to-mesenchymal transition. Breast Cancer Res. 2011, 13, doi:10.1186/bcr2876.
46. Wu, Y.; Zhou, B.P. Tnf-alpha/nf-kappab/snail pathway in cancer cell migration and invasion. Br. J. Cancer 2010, 102, 639-644.
47. Weaver, A.M. Invadopodia: Specialized cell structures for cancer invasion. Clin. Exp. Metastasis 2006, 23, 97-105.
48. Jiang, P.; Enomoto, A.; Takahashi, M. Cell biology of the movement of breast cancer cells: Intracellular signalling and the actin cytoskeleton. Cancer Lett. 2009, 284, 122-130.
49. Bae, Y.H.; Ding, Z.; Das, T.; Wells, A.; Gertler, F.; Roy, P. Profilin1 regulates pi(3,4)p2 and lamellipodin accumulation at the leading edge thus influencing motility of mda-mb-231 cells. Proc. Natl. Acad. Sci. USA 2010, 107, 21547-21552.
50. Bae, Y.H.; Ding, Z.; Zou, L.; Wells, A.; Gertler, F.; Roy, P. Loss of profilin-1 expression enhances breast cancer cell motility by ena/vasp proteins. J. Cell. Physiol. 2009, 219, 354-364.
51. Gertler, F.; Condeelis, J. Metastasis: Tumor cells becoming menacing. Trends Cell Biol. 2011, 21, 81-90.
52. Yilmaz, M.; Christofori, G. Mechanisms of motility in metastasizing cells. Mol. Cancer Res. 2010, 8, 629-642.
53. Sahai, E. Illuminating the metastatic process. Nat. Rev. Cancer 2007, 7, 737-749.
54. Longatto Filho, A.; Lopes, J.M.; Schmitt, F.C. Angiogenesis and breast cancer. J. Oncol. 2010, 2010, 576384:1-576384:7.
55. Carpini, J.D.; Karam, A.K.; Montgomery, L. Vascular endothelial growth factor and its relationship to the prognosis and treatment of breast, ovarian, and cervical cancer. Angiogenesis 2010, 13, 43-58.
56. Chakraborty, G.; Rangaswami, H.; Jain, S.; Kundu, G.C. Hypoxia regulates cross-talk between syk and lck leading to breast cancer progression and angiogenesis. J. Biol. Chem. 2006, 281, 11322-11331.
57. Pollard, J.W. Macrophages define the invasive microenvironment in breast cancer. J. Leukoc. Biol. 2008, 84, 623-630.
58. Ronnov-Jessen, L.; Bissell, M.J. Breast cancer by proxy: Can the microenvironment be both the cause and consequence? Trends Mol. Med. 2009, 15, 5-13.
59. McSherry, E.A.; Donatello, S.; Hopkins, A.M.; McDonnell, S. Molecular basis of invasion in breast cancer. Cell. Mol. Life Sci. 2007, 64, 3201-3218.
60. Hu, M.; Polyak, K. Molecular characterisation of the tumour microenvironment in breast cancer. Eur. J. Cancer 2008, 44, 2760-2765.
61. Radisky, E.S.; Radisky, D.C. Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer. J. Mammary Gland Biol. Neoplasia 2010, 15, 201-212.
62. Kohrmann, A.; Kammerer, U.; Kapp, M.; Dietl, J.; Anacker, J. Expression of matrix metalloproteinases (mmps) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature. BMC Cancer 2009, 9, 188:1-188:20.
63. Bostrom, P.; Soderstrom, M.; Vahlberg, T.; Soderstrom, K.O.; Roberts, P.J.; Carpen, O.; Hirsimaki, P. Mmp-1 expression has an independent prognostic value in breast cancer. BMC Cancer 2011, 11, 348:1-348:8.
64. Choi, J.Y.; Jang, Y.S.; Min, S.Y.; Song, J.Y. Overexpression of mmp-9 and hif-1alpha in breast cancer cells under hypoxic conditions. J. Breast Cancer 2011, 14, 88-95.
65. Zhang, B.; Liu, Y.X.; Cao, W.F.; Cao, X.C.; Ning, L.S.; Hao, X.S. Relationship between the expression of matrix metalloproteinase-13 protein and other biomarkers, prognosis in invasive breast cancer. Zhonghua Bing Li Xue Za Zhi 2008, 37, 471-476.
66. Stark, A.M.; Anuszkiewicz, B.; Mentlein, R.; Yoneda, T.; Mehdorn, H.M.; Held-Feindt, J. Differential expression of matrix metalloproteinases in brain- and bone-seeking clones of metastatic mda-mb-231 breast cancer cells. J. Neurooncol. 2007, 81, 39-48.
67. Denhardt, D.T.; Feng, B.; Edwards, D.R.; Cocuzzi, E.T.; Malyankar, U.M. Tissue inhibitor of metalloproteinases (timp, aka epa): Structure, control of expression and biological functions. Pharmacol. Ther. 1993, 59, 329-341.
68. Nguyen, Q.; Willenbrock, F.; Cockett, M.I.; O'Shea, M.; Docherty, A.J.; Murphy, G. Different domain interactions are involved in the binding of tissue inhibitors of metalloproteinases to stromelysin-1 and gelatinase a. Biochemistry 1994, 33, 2089-2095.
69. Vempati, P.; Karagiannis, E.D.; Popel, A.S. A biochemical model of matrix metalloproteinase 9 activation and inhibition. J. Biol. Chem. 2007, 282, 37585-37596.
70. O'Connell, J.P.; Willenbrock, F.; Docherty, A.J.; Eaton, D.; Murphy, G. Analysis of the role of the cooh-terminal domain in the activation, proteolytic activity, and tissue inhibitor of metalloproteinase interactions of gelatinaseb. J. Biol. Chem. 1994, 269, 14967-14973.
71. Knauper, V.; Lopez-Otin, C.; Smith, B.; Knight, G.; Murphy, G. Biochemical characterization of human collagenase-3. J. Biol. Chem. 1996, 271, 1544-1550.
72. Stratmann, B.; Farr, M.; Tschesche, H. Characterization of c-terminally truncated human tissue inhibitor of metalloproteinases-4 expressed in pichia pastoris. Biol. Chem. 2001, 382, 987-991.
73. Hardy, K.M.; Booth, B.W.; Hendrix, M.J.; Salomon, D.S.; Strizzi, L. Erbb/egf signaling and emt in mammary development and breast cancer. J. Mammary Gland Biol. Neoplasia 2010, 15, 191-199.
74. Raja, W.K.; Gligorijevic, B.; Wyckoff, J.; Condeelis, J.S.; Castracane, J. A new chemotaxis device for cell migration studies. Integr. Biol. (Camb) 2010, 2, 696-706.
75. Wesche, J.; Haglund, K.; Haugsten, E.M. Fibroblast growth factors and their receptors in cancer. Biochem. J. 2011, 437, 199-213.
76. Scollen, S.; Luccarini, C.; Baynes, C.; Driver, K.; Humphreys, M.K.; Garcia-Closas, M.; Figueroa, J.; Lissowska, J.; Pharoah, P.D.; Easton, D.F., et al. Tgf-beta signaling pathway and breast cancer susceptibility. Cancer Epidemiol. Biomark. Prev. 2011, 20, 1112-1119.
77. Swaminathan, V.; Mythreye, K.; O'Brien, E.T.; Berchuck, A.; Blobe, G.C.; Superfine, R. Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines. Cancer Res. 2011, 71, 5075-5080.
78. Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell 2000, 100, 57-70.
79. Wendt, M.K.; Taylor, M.A.; Schiemann, B.J.; Schiemann, W.P. Down-regulation of epithelial cadherin is required to initiate metastatic outgrowth of breast cancer. Mol. Biol. Cell 2011, 22, 2423-2435.
80. Morozevich, G.; Kozlova, N.; Cheglakov, I.; Ushakova, N.; Berman, A. Integrin alpha5beta1 controls invasion of human breast carcinoma cells by direct and indirect modulation of mmp-2 collagenase activity. Cell Cycle 2009, 8, 2219-2225.
81. Polyak, K.; Kalluri, R. The role of the microenvironment in mammary gland development and cancer. Cold Spring Harb. Perspect. Biol. 2010, 2, a003244:1-a003244:14.
82. Robinson, B.D.; Sica, G.L.; Liu, Y.F.; Rohan, T.E.; Gertler, F.B.; Condeelis, J.S.; Jones, J.G. Tumor microenvironment of metastasis in human breast carcinoma: A potential prognostic marker linked to hematogenous dissemination. Clin. Cancer Res. 2009, 15, 2433-2441.
83. Yizraeli, M.L.; Weihs, D. Time-dependent micromechanical responses of breast cancer cells and adjacent fibroblasts to electric treatment. Cell Biochem. Biophys. 2011, in press.
84. Kashani, I.; Barvarestani, M.; Etesam, F.; Shokrgozar, M.; Abdolvahabi, M.; Haddad, P.; Noori Mokohi, M.H.; Hosseinf, M. Human preadipocytes inhibit proliferation of MCF-7 breast cancer cell line. Acta Medica Iran. 2006, 44, 291-298.
85. Krause, S.; Maffini, M.V.; Soto, A.M.; Sonnenschein, C. The microenvironment determines the breast cancer cells' phenotype: Organization of mcf7 cells in 3d cultures. BMC Cancer 2010, 10, 263:1-263:13.
86. Krause, S.; Maffini, M.V.; Soto, A.M.; Sonnenschein, C. A novel 3d in vitro culture model to study stromal-epithelial interactions in the mammary gland. Tissue Eng. Part C Methods 2008, 14, 261-271.
87. Dirat, B.; Bochet, L.; Dabek, M.; Daviaud, D.; Dauvillier, S.; Majed, B.; Wang, Y.Y.; Meulle, A.; Salles, B.; Le Gonidec, S., et al. Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res. 2011, 71, 2455-2465.
88. Poczobutt, J.M.; Tentler, J.; Lu, X.; Schedin, P.J.; Gutierrez-Hartmann, A. Benign mammary epithelial cells enhance the transformed phenotype of human breast cancer cells. BMC Cancer 2010, 10, 373:1-373:17.
89. Sasser, A.K.; Mundy, B.L.; Smith, K.M.; Studebaker, A.W.; Axel, A.E.; Haidet, A.M.; Fernandez, S.A.; Hall, B.M. Human bone marrow stromal cells enhance breast cancer cell growth rates in a cell line-dependent manner when evaluated in 3d tumor environments. Cancer Lett. 2007, 254, 255-264.
90. Ingthorsson, S.; Sigurdsson, V.; Fridriksdottir, A., Jr.; Jonasson, J.G.; Kjartansson, J.; Magnusson, M.K.; Gudjonsson, T. Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3d culture. BMC Res. Notes 2010, 3, 184:1-184:12.
91. Dimri, G.P. What has senescence got to do with cancer? Cancer Cell 2005, 7, 505-512.
92. Yaar, M.; Eller, M.S.; Panova, I.; Kubera, J.; Wee, L.H.; Cowan, K.H.; Gilchrest, B.A. Telomeric DNA induces apoptosis and senescence of human breast carcinoma cells. Breast Cancer Res. 2007, 9, R13:1-R13:13.
93. Huang, M.; Whang, P.; Lewicki, P.; Mitchell, B.S. Cyclopentenyl cytosine induces senescence in breast cancer cells through the nucleolar stress response and activation of p53. Mol. Pharmacol. 2011, 80, 40-48.
94. Callahan, R.; Hurvitz, S. Human epidermal growth factor receptor-2-positive breast cancer: Current management of early, advanced, and recurrent disease. Curr. Opin. Obstet. Gynecol. 2011, 23, 37-43.
95. Sun, J. Matrix metalloproteinases and tissue inhibitor of metalloproteinases are essential for the inflammatory response in cancer cells. J. Signal Transduct. 2010, 2010, 985132:1-985132:7.
96. Koziczak, M.; Holbro, T.; Hynes, N.E. Blocking of fgfr signaling inhibits breast cancer cell proliferation through downregulation of d-type cyclins. Oncogene 2004, 23, 3501-3508.
97. Eckert, M.A.; Yang, J. Targeting invadopodia to block breast cancer metastasis. Oncotarget 2011, 2, 562-568.
98. Subbaram, S.; Dipersio, C.M. Integrin alpha3beta1 as a breast cancer target. Expert Opin. Ther. Targets 2011, in press.
99. Ju, J.H.; Jang, K.; Lee, K.M.; Kim, M.; Kim, J.; Yi, J.Y.; Noh, D.Y.; Shin, I. Cd24 enhances DNA damage-induced apoptosis by modulating nf-{kappa}b signaling in cd44 expressing breast cancer cells. Carcinogenesis 2011, doi: 10.1093/carcin/bgr173.
100. Joyce, J.A. Therapeutic targeting of the tumor microenvironment. Cancer Cell 2005, 7, 513-520.
101. Loh, Y.H.; Wu, Q.; Chew, J.L.; Vega, V.B.; Zhang, W.; Chen, X.; Bourque, G.; George, J.; Leong, B.; Liu, J., et al. The oct4 and nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat. Genet. 2006, 38, 431-440.
102. Pan, G.; Thomson, J.A. Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Res. 2007, 17, 42-49.
103. Hu, J.; Qin, K.; Zhang, Y.; Gong, J.; Li, N.; Lv, D.; Xiang, R.; Tan, X. Downregulation of transcription factor oct4 induces an epithelial-to-mesenchymal transition via enhancement of ca(2+) influx in breast cancer cells. Biochem. Biophys. Res. Commun. 2011, 411, 786-791.
104. Guo, Y.; Graham-Evans, B.; Broxmeyer, H.E. Murine embryonic stem cells secrete cytokines/growth modulators that enhance cell survival/anti-apoptosis and stimulate colony formation of murine hematopoietic progenitor cells. Stem Cells 2006, 24, 850-856.
105. Llanes-Fernández, L.; Álvarez-Goyanes, R.I.; del Carmen Arango-, M.; Alcocer-González, J.M.; Mojarrieta, J.C.; Pérez, X.E.; López, M.O.; Odio, S.F.; Camacho-Rodríguez, R.; Guerra-Yi, M.E., et al. Relationship between il-10 and tumor markers in breast cancer patients. Breast 2006, 15, 482-489.
106. Gerger, A.; Renner, W.; Langsenlehner, T.; Hofmann, G.; Knechtel, G.; Szkandera, J.; Samonigg, H.; Krippl, P.; Langsenlehner, U. Association of interleukin-10 gene variation with breast cancer prognosis. Breast Cancer Res. Treat. 2010, 119, 701-705.
107. Lacroix, M.; Siwek, B.; Marie, P.J.; Body, J.J. Production and regulation of interleukin-11 by breast cancer cells. Cancer Lett. 1998, 127, 29-35.
108. Hanavadi, S.; Martin, T.; Watkins, G.; Mansel, R.; Jiang, W. Expression of interleukin 11 and its receptor and their prognostic value in human breast cancer. Ann. Surg. Oncol. 2006, 13, 802-808.
109. Singer, C.F.; Kronsteiner, N.; Hudelist, G.; Marton, E.; Walter, I.; Kubista, M.; Czerwenka, K.; Schreiber, M.; Seifert, M.; Kubista, E. Interleukin 1 system and sex steroid receptor expression in human breast cancer: Interleukin 1alpha protein secretion is correlated with malignant phenotype. Clin. Cancer Res. 2003, 9, 4877-4883.
110. Liu, J.; Spence, M.J.; Wallace, P.M.; Forcier, K.; Hellstrom, I.; Vestal, R.E. Oncostatin m-specific receptor mediates inhibition of breast cancer cell growth and down-regulation of the c-myc proto-oncogene. Cell Growth Differ. 1997, 8, 667-676.
111. Liu, J.; Hadjokas, N.; Mosley, B.; Estrov, Z.; Spence, M.J.; Vestal, R.E. Oncostatin m-specific receptor expression and function in regulating cell proliferation of normal and malignant mammary epithelial cells. Cytokine 1998, 10, 295-302.
112. Jorcyk, C.L.; Holzer, R.G.; Ryan, R.E. Oncostatin m induces cell detachment and enhances the metastatic capacity of t-47d human breast carcinoma cells. Cytokine 2006, 33, 323-336.
113. Ulivi, P.; Zoli, W.; Medri, L.; Amadori, D.; Saragoni, L.; Barbanti, F.; Calistri, D.; Silvestrini, R. C-kit and scf expression in normal and tumor breast tissue. Breast Cancer Res. Treat. 2004, 83, 33-42.
114. Hines, S.J.; Litz, J.S.; Krystal, G.W. Coexpression of c-kit and stem cell factor in breast cancer results in enhanced sensitivity to members of the egf family of growth factors. Breast Cancer Res. Treat. 1999, 58, 1-10.
115. Roland, C.L.; Dineen, S.P.; Lynn, K.D.; Sullivan, L.A.; Dellinger, M.T.; Sadegh, L.; Sullivan, J.P.; Shames, D.S.; Brekken, R.A. Inhibition of vascular endothelial growth factor reduces angiogenesis and modulates immune cell infiltration of orthotopic breast cancer xenografts. Mol. Cancer Ther. 2009, 8, 1761-1771.
116. Bieche, I.; Chavey, C.; Andrieu, C.; Busson, M.; Vacher, S.; Le Corre, L.; Guinebretiere, J.M.; Burlinchon, S.; Lidereau, R.; Lazennec, G. Cxc chemokines located in the 4q21 region are up-regulated in breast cancer. Endocr. Relat. Cancer 2007, 14, 1039-1052.
117. Walser, T.C.; Rifat, S.; Ma, X.; Kundu, N.; Ward, C.; Goloubeva, O.; Johnson, M.G.; Medina, J.C.; Collins, T.L.; Fulton, A.M. Antagonism of cxcr3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res. 2006, 66, 7701-7707.
118. Kim, M.Y.; Oskarsson, T.; Acharyya, S.; Nguyen, D.X.; Zhang, X.H.; Norton, L.; Massague, J. Tumor self-seeding by circulating cancer cells. Cell 2009, 139, 1315-1326.
119. Qian, B.Z.; Li, J.; Zhang, H.; Kitamura, T.; Zhang, J.; Campion, L.R.; Kaiser, E.A.; Snyder, L.A.; Pollard, J.W. Ccl2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 2011, 475, 222-225.
120. Nath, A.; Chattopadhya, S.; Chattopadhyay, U.; Sharma, N.K. Macrophage inflammatory protein (mip)1alpha and mip1beta differentially regulate release of inflammatory cytokines and generation of tumoricidal monocytes in malignancy. Cancer Immunol. Immunother. 2006, 55, 1534-1541.
121. Ohara, M.; Yamaguchi, Y.; Matsuura, K.; Murakami, S.; Arihiro, K.; Okada, M. Possible involvement of regulatory t cells in tumor onset and progression in primary breast cancer. Cancer Immunol. Immunother. 2009, 58, 441-447.
122. Bussard, K.M.; Venzon, D.J.; Mastro, A.M. Osteoblasts are a major source of inflammatory cytokines in the tumor microenvironment of bone metastatic breast cancer. J. Cell. Biochem. 2010, 111, 1138-1148.
123. Gomes, E.M.; Rodrigues, M.S.; Phadke, A.P.; Butcher, L.D.; Starling, C.; Chen, S.; Chang, D.; Hernandez-Alcoceba, R.; Newman, J.T.; Stone, M.J., et al. Antitumor activity of an oncolytic adenoviral-cd40 ligand (cd154) transgene construct in human breast cancer cells. Clin. Cancer Res. 2009, 15, 1317-1325.
124. Lee, S.J.; Yoo, H.J.; Bae, Y.S.; Kim, H.J.; Lee, S.T. Timp-1 inhibits apoptosis in breast carcinoma cells via a pathway involving pertussis toxin-sensitive g protein and c-src. Biochem. Biophys. Res. Commun. 2003, 312, 1196-1201.
125. Michalska, A.E. Chapter 1, Unit1C.3 Isolation and propagation of mouse embryonic fibroblasts and preparation of mouse embryonic feeder layer cells. In Current Protocols in Stem Cell Biology; John Wiley and Sons, Inc.: Hoboken, NJ, USA, 2007.
126. Amit, M.; Margulets, V.; Segev, H.; Shariki, K.; Laevsky, I.; Coleman, R.; Itskovitz-Eldor, J. Human feeder layers for human embryonic stem cells. Biol. Reprod. 2003, 68, 2150-2156.
127. Lin, S.; Talbot, P. Methods for culturing mouse and human embryonic stem cells. Methods Mol. Biol. 2011, 690, 31-56.
128. Abraham, S.; Sheridan, S.D.; Miller, B.; Rao, R.R. Stable propagation of human embryonic and induced pluripotent stem cells on decellularized human substrates. Biotechnol. Prog. 2010, 26, 1126-1134.
129. Hirai, H.; Karian, P.; Kikyo, N. Regulation of embryonic stem cell self-renewal and pluripotency by leukaemia inhibitory factor. Biochem. J. 2011, 438, 11-23.
130. Levenstein, M.E.; Ludwig, T.E.; Xu, R.H.; Llanas, R.A.; Van Den Heuvel-Kramer, K.; Manning, D.; Thomson, J.A. Basic fibroblast growth factor support of human embryonic stem cell self-renewal. Stem Cells 2006, 24, 568-574.
131. Wang, L.; Schulz, T.C.; Sherrer, E.S.; Dauphin, D.S.; Shin, S.; Nelson, A.M.; Ware, C.B.; Zhan, M.; Song, C.Z.; Chen, X., et al. Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and erbb2 receptor signaling. Blood 2007, 110, 4111-4119.
132. Gerecht, S.; Burdick, J.A.; Ferreira, L.S.; Townsend, S.A.; Langer, R.; Vunjak-Novakovic, G. Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells. Proc. Natl. Acad. Sci. USA 2007, 104, 11298-11303.
133. Siti-Ismail, N.; Bishop, A.E.; Polak, J.M.; Mantalaris, A. The benefit of human embryonic stem cell encapsulation for prolonged feeder-free maintenance. Biomaterials 2008, 29, 3946-3952.
134. Wang, X.; Wang, W.; Ma, J.; Guo, X.; Yu, X.; Ma, X. Proliferation and differentiation of mouse embryonic stem cells in apa microcapsule: A model for studying the interaction between stem cells and their niche. Biotechnol. Prog. 2006, 22, 791-800.
135. Li, Z.; Leung, M.; Hopper, R.; Ellenbogen, R.; Zhang, M. Feeder-free self-renewal of human embryonic stem cells in 3d porous natural polymer scaffolds. Biomaterials 2010, 31, 404-412.
136. Raof, N.A.; Padgen, M.R.; Gracias, A.R.; Bergkvist, M.; Xie, Y. One-dimensional self-assembly of mouse embryonic stem cells using an array of hydrogel microstrands. Biomaterials 2011, 32, 4498-4505.
137. Peng, S.; Hua, J.; Cao, X.; Wang, H. Gelatin induces trophectoderm differentiation of mouse embryonic stem cells. Cell Biol. Int. 2011, 35, 587-591.
138. Farzaneh, Z.; Pournasr, B.; Ebrahimi, M.; Aghdami, N.; Baharvand, H. Enhanced functions of human embryonic stem cell-derived hepatocyte-like cells on three-dimensional nanofibrillar surfaces. Stem Cell Rev. 2010, 6, 601-610.
139. Mahairaki, V.; Lim, S.H.; Christopherson, G.T.; Xu, L.; Nasonkin, I.; Yu, C.; Mao, H.Q.; Koliatsos, V.E. Nanofiber matrices promote the neuronal differentiation of human embryonic stem cell-derived neural precursors in vitro. Tissue Eng. Part A 2011, 17, 855-863.
140. Smith, L.A.; Liu, X.; Hu, J.; Ma, P.X. The enhancement of human embryonic stem cell osteogenic differentiation with nano-fibrous scaffolding. Biomaterials 2010, 31, 5526-5535.
141. Smith, L.A.; Liu, X.; Hu, J.; Ma, P.X. The influence of three-dimensional nanofibrous scaffolds on the osteogenic differentiation of embryonic stem cells. Biomaterials 2009, 30, 2516-2522.
142. Kang, X.; Xie, Y.; Powell, H.M.; James Lee, L.; Belury, M.A.; Lannutti, J.J.; Kniss, D.A. Adipogenesis of murine embryonic stem cells in a three-dimensional culture system using electrospun polymer scaffolds. Biomaterials 2007, 28, 450-458.
143. Xie, J.; Willerth, S.M.; Li, X.; Macewan, M.R.; Rader, A.; Sakiyama-Elbert, S.E.; Xia, Y. The differentiation of embryonic stem cells seeded on electrospun nanofibers into neural lineages. Biomaterials 2009, 30, 354-362.
144. Schiele, N.R.; Corr, D.T.; Huang, Y.; Raof, N.A.; Xie, Y.; Chrisey, D.B. Laser-based direct-write techniques for cell printing. Biofabrication 2010, 2, doi:10.1088/1758-5082/2/3/032001.
145. Postovit, L.M.; Seftor, E.A.; Seftor, R.E.; Hendrix, M.J. Influence of the microenvironment on melanoma cell fate determination and phenotype. Cancer Res. 2006, 66, 7833-7836.
146. Hendrix, M.J.; Seftor, E.A.; Seftor, R.E.; Kasemeier-Kulesa, J.; Kulesa, P.M.; Postovit, L.M. Reprogramming metastatic tumour cells with embryonic microenvironments. Nat. Rev. Cancer 2007, 7, 246-255.
147. Kasemeier-Kulesa, J.C.; Teddy, J.M.; Postovit, L.M.; Seftor, E.A.; Seftor, R.E.; Hendrix, M.J.; Kulesa, P.M. Reprogramming multipotent tumor cells with the embryonic neural crest microenvironment. Dev. Dyn. 2008, 237, 2657-2666.
148. Illmensee, K.; Mintz, B. Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts. Proc. Natl. Acad. Sci. USA 1976, 73, 549-553.
149. Pierce, G.B.; Pantazis, C.G.; Caldwell, J.E.; Wells, R.S. Specificity of the control of tumor formation by the blastocyst. Cancer Res. 1982, 42, 1082-1087.
150. Lee, L.M.; Seftor, E.A.; Bonde, G.; Cornell, R.A.; Hendrix, M.J. The fate of human malignant melanoma cells transplanted into zebrafish embryos: Assessment of migration and cell division in the absence of tumor formation. Dev. Dyn. 2005, 233, 1560-1570.
151. Diez-Torre, A.; Andrade, R.; Eguizabal, C.; Lopez, E.; Arluzea, J.; Silio, M.; Arechaga, J. Reprogramming of melanoma cells by embryonic microenvironments. Int. J. Dev. Biol. 2009, 53, 1563-1568.
152. Ma, F.; Zhou, L.; Fang, L.Q.; Bai, J.; Zhao, J.; Wang, Y.; Wang, Z.B. Effect of mid-late mouse fetus' microenvironment on the growth of tumor cells after intrauterine transplantation. Cell Biol. Int. 2007, 31, 592-598.
153. Patton, E.E.; Widlund, H.R.; Kutok, J.L.; Kopani, K.R.; Amatruda, J.F.; Murphey, R.D.; Berghmans, S.; Mayhall, E.A.; Traver, D.; Fletcher, C.D., et al. Braf mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr. Biol. 2005, 15, 249-254.
154. Kelleher, F.; Fennelly, D.; Rafferty, M. Common critical pathways in embryogenesis and cancer. Acta Oncol. 2006, 45, 375-388.
155. Dreesen, O.; Brivanlou, A. Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev. Rep. 2007, 3, 7-17.
156. Al-Hajj, M.; Wicha, M.S.; Benito-Hernandez, A.; Morrison, S.J.; Clarke, M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 2003, 100, 3983-3988.
157. Marcato, P.; Dean, C.A.; Pan, D.; Araslanova, R.; Gillis, M.; Joshi, M.; Helyer, L.; Pan, L.; Leidal, A.; Gujar, S., et al. Aldehyde dehydrogenase activity of breast cancer stem cells is primarily due to isoform aldh1a3 and its expression is predictive of metastasis. Stem Cells 2011, 29, 32-45.
158. Charafe-Jauffret, E.; Ginestier, C.; Birnbaum, D. Breast cancer stem cells: Tools and models to rely on. BMC Cancer 2009, 9, 202:1-202:10.
159. Liu, S.; Ginestier, C.; Ou, S.J.; Clouthier, S.G.; Patel, S.H.; Monville, F.; Korkaya, H.; Heath, A.; Dutcher, J.; Kleer, C.G., et al. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res. 2011, 71, 614-624.
160. Ginestier, C.; Charafe-Jauffret, E.; Birnbaum, D. Targeting breast cancer stem cells: Fishing season open. Breast Cancer Res. 2010, 12, 312:-312:2.
161. Liu, S.; Wicha, M.S. Targeting breast cancer stem cells. J. Clin. Oncol. 2010, 28, 4006-4012.
162. Korkaya, H.; Liu, S.; Wicha, M.S. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J. Clin. Invest. 2011, 121, 3804-3809.
163. Velasco-Velazquez, M.A.; Popov, V.M.; Lisanti, M.P.; Pestell, R.G. The role of breast cancer stem cells in metastasis and therapeutic implications. Am. J. Pathol. 2011, 179, 2-11.
164. Wong, D.J.; Liu, H.; Ridky, T.W.; Cassarino, D.; Segal, E.; Chang, H.Y. Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2008, 2, 333-344.
165. Somervaille, T.C.P.; Matheny, C.J.; Spencer, G.J.; Iwasaki, M.; Rinn, J.L.; Witten, D.M.; Chang, H.Y.; Shurtleff, S.A.; Downing, J.R.; Cleary, M.L. Hierarchical maintenance of mll myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells. Cell Stem Cell 2009, 4, 129-140.
166. Postovit, L.M.; Seftor, E.A.; Seftor, R.E.; Hendrix, M.J. A three-dimensional model to study the epigenetic effects induced by the microenvironment of human embryonic stem cells. Stem Cells 2006, 24, 501-505.
167. Abbott, D.E.; Bailey, C.M.; Postovit, L.M.; Seftor, E.A.; Margaryan, N.; Seftor, R.E.; Hendrix, M.J. The epigenetic influence of tumor and embryonic microenvironments: How different are they? Cancer Microenviron. 2008, 1, 13-21.
168. Ben-Porath, I.; Thomson, M.W.; Carey, V.J.; Ge, R.; Bell, G.W.; Regev, A.; Weinberg, R.A. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat. Genet. 2008, 40, 499-507.
169. Raof, N.A.; Raja, W.K.; Castracane, J.; Xie, Y. Bioengineering embryonic stem cell microenvironments for exploring inhibitory effects on metastatic breast cancer cells. Biomaterials 2011, 32, 4130-4139.
170. Kievit, F.M.; Florczyk, S.J.; Leung, M.C.; Veiseh, O.; Park, J.O.; Disis, M.L.; Zhang, M. Chitosan-alginate 3d scaffolds as a mimic of the glioma tumor microenvironment. Biomaterials 2010, 31, 5903-5910.
171. Chen, M.C.; Gupta, M.; Cheung, K.C. Alginate-based microfluidic system for tumor spheroid formation and anticancer agent screening. Biomed. Microdevices 2010, 12, 647-654.
172. Akeda, K.; Nishimura, A.; Satonaka, H.; Shintani, K.; Kusuzaki, K.; Matsumine, A.; Kasai, Y.; Masuda, K.; Uchida, A. Three-dimensional alginate spheroid culture system of murine osteosarcoma. Oncol. Rep. 2009, 22, 997-1003.
173. Plunkett, M.L.; Hailey, J.A. An in vivo quantitative angiogenesis model using tumor cells entrapped in alginate. Lab. Invest. 1990, 62, 510-517.
174. Yamada, K.M.; Cukierman, E. Modeling tissue morphogenesis and cancer in 3d. Cell 2007, 130, 601-610.
175. Gautier, A.; Carpentier, B.; Dufresne, M.; Vu Dinh, Q.; Paullier, P.; Legallais, C. Impact of alginate type and bead diameter on mass transfers and the metabolic activities of encapsulated c3a cells in bioartificial liver applications. Eur. Cell Mater. 2011, 21, 94-106.
176. Strand, B.L.; Morch, Y.A.; Syvertsen, K.R.; Espevik, T.; Skjak-Braek, G. Microcapsules made by enzymatically tailored alginate. J. Biomed. Mater. Res. A 2003, 64, 540-550.
177. Tan, C.S.; Jejurikar, A.; Rai, B.; Bostrom, T.; Lawrie, G.; Grondahl, L. Encapsulation of a glycosaminoglycan in hydroxyapatite/alginate capsules. J. Biomed. Mater. Res. A 2009, 91, 866-877.
178. Hannouche, D.; Terai, H.; Fuchs, J.R.; Terada, S.; Zand, S.; Nasseri, B.A.; Petite, H.; Sedel, L.; Vacanti, J.P. Engineering of implantable cartilaginous structures from bone marrow-derived mesenchymal stem cells. Tissue Eng. 2007, 13, 87-99.
179. Wang, N.; Adams, G.; Buttery, L.; Falcone, F.H.; Stolnik, S. Alginate encapsulation technology supports embryonic stem cells differentiation into insulin-producing cells. J. Biotechnol. 2009, 144, 304-312.
180. Hwang, Y.S.; Cho, J.; Tay, F.; Heng, J.Y.; Ho, R.; Kazarian, S.G.; Williams, D.R.; Boccaccini, A.R.; Polak, J.M.; Mantalaris, A. The use of murine embryonic stem cells, alginate encapsulation, and rotary microgravity bioreactor in bone tissue engineering. Biomaterials 2009, 30, 499-507.
181. Maguire, T.; Davidovich, A.E.; Wallenstein, E.J.; Novik, E.; Sharma, N.; Pedersen, H.; Androulakis, I.P.; Schloss, R.; Yarmush, M. Control of hepatic differentiation via cellular aggregation in an alginate microenvironment. Biotechnol. Bioeng. 2007, 98, 631-644.
182. Zhao, L.; Tang, M.; Weir, M.D.; Detamore, M.S.; Xu, H.H. Osteogenic media and rhbmp-2-induced differentiation of umbilical cord mesenchymal stem cells encapsulated in alginate microbeads and integrated in an injectable calcium phosphate-chitosan fibrous scaffold. Tissue Eng. Part A 2011, 17, 969-979.
183. Bai, H.Y.; Chen, G.A.; Mao, G.H.; Song, T.R.; Wang, Y.X. Three step derivation of cartilage like tissue from human embryonic stem cells by 2d-3d sequential culture in vitro and further implantation in vivo on alginate/plga scaffolds. J. Biomed. Mater. Res. A 2010, 94, 539-546.
184. Trivedi, N.; Keegan, M.; Steil, G.M.; Hollister-Lock, J.; Hasenkamp, W.M.; Colton, C.K.; Bonner-Weir, S.; Weir, G.C. Islets in alginate macrobeads reverse diabetes despite minimal acute insulin secretory responses. Transplantation 2001, 71, 203-211.
185. Dufrane, D.; Goebbels, R.M.; Gianello, P. Alginate macroencapsulation of pig islets allows correction of streptozotocin-induced diabetes in primates up to 6 months without immunosuppression. Transplantation 2010, 90, 1054-1062.
186. Dufrane, D.; Goebbels, R.M.; Saliez, A.; Guiot, Y.; Gianello, P. Six-month survival of microencapsulated pig islets and alginate biocompatibility in primates: Proof of concept. Transplantation 2006, 81, 1345-1353.
187. Fritschy, W.M.; Wolters, G.H.; van Schilfgaarde, R. Effect of alginate-polylysine-alginate microencapsulation on in vitro insulin release from rat pancreatic islets. Diabetes 1991, 40, 37-43.
188. Xu, M.; Wang, X.; Yan, Y.; Yao, R.; Ge, Y. An cell-assembly derived physiological 3d model of the metabolic syndrome, based on adipose-derived stromal cells and a gelatin/alginate/fibrinogen matrix. Biomaterials 2010, 31, 3868-3877.
189. Ruvinov, E.; Leor, J.; Cohen, S. The promotion of myocardial repair by the sequential delivery of igf-1 and hgf from an injectable alginate biomaterial in a model of acute myocardial infarction. Biomaterials 2011, 32, 565-578.