Engineering a humanized bone organ model in mice to study bone metastases

Nature Protocols

Volumn 12, Issue 4, 2017, Pages 639-663

  Martine, Laure C ^a   Holzapfel, Boris M ^a,b   McGovern, Jacqui A ^a   Wagner, Ferdinand ^a,c,d   Quent, Verena M ^a,e   Hesami, Parisa ^a   Wunner, Felix M ^a   Vaquette, Cedryck ^a   De Juan Pardo, Elena M ^a   Brown, Toby D ^a   Nowlan, Bianca ^f   Wu, Dan Jing ^a,g   Hutmacher, Cosmo Orlando ^a   Moi, Davide ^f   Oussenko, Tatiana ^e   Piccinini, Elia ^e   Zandstra, Peter W ^e   Mazzieri, Roberta ^f   Lévesque, Jean Pierre ^b,e   Dalton, Paul D ^a,h   Taubenberger, Anna V ^a,i   Hutmacher, Dietmar W ^a,j   more..

^a QUEENSLAND UNIVERSITY OF TECHNOLOGY   (Australia)

^b UNIVERSITY OF WÜRZBURG   (Germany)

^c LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^d CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^e UNIVERSITY OF QUEENSLAND   (Australia)

^f EINDHOVEN UNIVERSITY OF TECHNOLOGY   (Netherlands)

^g UNIVERSITY OF TORONTO   (Canada)

^h DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

ⁱ GEORGIA INSTITUTE OF TECHNOLOGY   (United States)

^j TECHNICAL UNIVERSITY OF MUNICH   (Germany)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BONE CELL; BONE DEVELOPMENT; BONE METASTASIS; BONE TISSUE; BONE TISSUE ENGINEERING; CONTROLLED STUDY; EXTRACELLULAR MATRIX; FEMALE; FETUS; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL; HUMAN; HUMAN CELL; MALE; MOUSE; NONHUMAN; OSTEOBLAST; TISSUE ENGINEERING; TISSUE SCAFFOLD; TUMOR MICROENVIRONMENT; ADENOCARCINOMA; ANIMAL; BONE; BONE TUMOR; BREAST TUMOR; DEVICES; DISEASE MODEL; DRUG EFFECTS; ELECTRICITY; HEMATOPOIETIC STEM CELL TRANSPLANTATION; METABOLISM; PATHOLOGY; PROCEDURES; PROSTATE TUMOR; SECONDARY;

BMP7 PROTEIN, HUMAN; OSTEOGENIC PROTEIN 1;

ADENOCARCINOMA; ANIMALS; BONE AND BONES; BONE MORPHOGENETIC PROTEIN 7; BONE NEOPLASMS; BREAST NEOPLASMS; DISEASE MODELS, ANIMAL; ELECTRICITY; EXTRACELLULAR MATRIX; FEMALE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; MALE; MICE; PROSTATIC NEOPLASMS; TISSUE ENGINEERING;

EID: 85014458511     PISSN: 17542189     EISSN: 17502799     Source Type: Journal    
DOI: 10.1038/nprot.2017.002     Document Type: Article

References (90)

1. Coleman, R.E. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin. Cancer Res. 12, 6243s-6249s (2006).
2. Taubenberger, A.V. In vitro microenvironments to study breast cancer bone colonisation. Adv. Drug Deliv. Rev. 79-80, 135-144 (2014).
3. Villasante, A., Marturano-Kruik, A. & Vunjak-Novakovic, G. Bioengineered human tumor within a bone niche. Biomaterials 35, 5785-5794 (2014).
4. Tan, P.H., Aung, K.Z., Toh, S.L., Goh, J.C. & Nathan, S.S. Three-dimensional porous silk tumor constructs in the approximation of in vivo osteosarcoma physiology. Biomaterials 32, 6131-6137 (2011).
5. Hamdi, D.H. et al. In vitro engineering of human 3D chondrosarcoma: A preclinical model relevant for investigations of radiation quality impact. BMC Cancer 15, 579 (2015).
6. Khanna, C. & Hunter, K. Modeling metastasis in vivo. Carcinogenesis 26, 513-523 (2005).
7. Gupta, P.B. & Kuperwasser, C. Disease models of breast cancer. Drug Discov. Today Dis. Models 1, 9-16 (2004).
8. Ek, E.T., Dass, C.R. & Choong, P.F. Commonly used mouse models of osteosarcoma. Crit. Rev. Oncol. Hematol. 60, 1-8 (2006).
9. Janeway, K.A. & Walkley, C.R. Modeling human osteosarcoma in the mouse: from bedside to bench. Bone 47, 859-865 (2010).
10. Kretschmann, K.L. & Welm, A.L. Mouse models of breast cancer metastasis to bone. Cancer Metastasis Rev. 31, 579-583 (2012).
11. Singh, A.S. & Figg, W.D. In vivo models of prostate cancer metastasis to bone. J. Urol. 174, 820-826 (2005).
12. Tolcher, A.W. et al. Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer. J. Clin. Oncol. 17, 478-484 (1999).
13. Kostenuik, P.J. et al. Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J. Bone Miner. Res. 24, 182-195 (2009).
14. Shtivelman, E. & Namikawa, R. Species-specific metastasis of human tumor cells in the severe combined immunodeficiency mouse engrafted with human tissue. Proc. Natl. Acad. Sci. USA 92, 4661-4665 (1995).
15. Nemeth, J.A. et al. Severe combined immunodeficient-hu model of human prostate cancer metastasis to human bone. Cancer Res. 59, 1987-1993 (1999).
16. Kuperwasser, C. et al. A mouse model of human breast cancer metastasis to human bone. Cancer Res. 65, 6130-6138 (2005).
17. Hesami, P. et al. A humanized tissue-engineered in vivo model to dissect interactions between human prostate cancer cells and human bone. Clin. Exp. Metastasis 31, 435-446 (2014).
18. Holzapfel, B.M. et al. Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone. Biomaterials 35, 4108-4115 (2014).
19. Thibaudeau, L. et al. A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone. Dis. Model. Mech. 7, 299-309 (2014).
20. Quent, V.M.C., Theodoropoulos, C., Hutmacher, D.W. & Reichert, J.C. Differential osteogenicity of multiple donor-derived human mesenchymal stem cells and osteoblasts in monolayer, scaffold-based 3D culture and in vivo. Biomed. Tech. 61, 253-266 (2016).
21. Hutmacher, D.W. Scaffolds in tissue engineering bone and cartilage. Biomaterials 21, 2529-2543 (2000).
22. Hutmacher, D.W., Schantz, J.T., Lam, C.X., Tan, K.C. & Lim, T.C. State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective. J. Tissue Eng. Regen. Med. 1, 245-260 (2007).
23. Hutmacher, D.W. & Cool, S. Concepts of scaffold-based tissue engineering-The rationale to use solid free-form fabrication techniques. J. Cell. Mol. Med. 11, 654-669 (2007).
24. Reichert, J.C. et al. A tissue engineering solution for segmental defect regeneration in load-bearing long bones. Sci. Transl. Med. 4, 141ra193 (2012).
25. Zhou, Y. et al. Combined marrow stromal cell-sheet techniques and high-strength biodegradable composite scaffolds for engineered functional bone grafts. Biomaterials 28, 814-824 (2007).
26. Brown, T.D. et al. Design and fabrication of tubular scaffolds via direct writing in a melt electrospinning mode. Biointerphases 7, 13 (2012).
27. Kolambkar, Y.M. et al. Spatiotemporal delivery of bone morphogenetic protein enhances functional repair of segmental bone defects. Bone 49, 485-492 (2011).
28. Hutmacher, D.W. & Dalton, P.D. Melt electrospinning. Chem. Asian J. 6, 44-56 (2011).
29. Vaquette, C. & Cooper-White, J.J. Increasing electrospun scaffold pore size with tailored collectors for improved cell penetration. Acta Biomater. 7, 2544-2557 (2011).
30. Brown, T.D., Dalton, P.D. & Hutmacher, D.W. Direct writing by way of melt electrospinning. Adv. Mater. 23, 5651-5657 (2011).
31. Farrugia, B.L. et al. Dermal fibroblast infiltration of poly(e-caprolactone) scaffolds fabricated by melt electrospinning in a direct writing mode. Biofabrication 5, 025001 (2013).
32. Vaquette, C., Ivanovski, S., Hamlet, S.M. & Hutmacher, D.W. Effect of culture conditions and calcium phosphate coating on ectopic bone formation. Biomaterials 34, 5538-5551 (2013).
33. Chatterjea, A., Meijer, G., van Blitterswijk, C. & de Boer, J. Clinical application of human mesenchymal stromal cells for bone tissue engineering. Stem Cells Int. 2010, 215625 (2010).
34. Kern, S., Eichler, H., Stoeve, J., Kluter, H. & Bieback, K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24, 1294-1301 (2006).
35. Reinisch, A. et al. Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation. Blood 125, 249-260 (2015).
36. Reichert, J.C., Quent, V.M., Noth, U. & Hutmacher, D.W. Ovine cortical osteoblasts outperform bone marrow cells in an ectopic bone assay. J. Tissue Eng. Regen. Med. 5, 831-844 (2011).
37. Dickhut, A. et al. Calcification or dedifferentiation: requirement to lock mesenchymal stem cells in a desired differentiation stage. J. Cell. Physiol. 219, 219-226 (2009).
38. Zhang, Z.Y. et al. Superior osteogenic capacity for bone tissue engineering of fetal compared with perinatal and adult mesenchymal stem cells. Stem Cells 27, 126-137 (2009).
39. Holzapfel, B.M. et al. Tissue engineered humanized bone supports human hematopoiesis in vivo. Biomaterials 61, 103-114 (2015).
40. Ooi, L.L., Zheng, Y., Stalgis-Bilinski, K. & Dunstan, C.R. The bone remodeling environment is a factor in breast cancer bone metastasis. Bone 48, 66-70 (2011).
41. Mastro, A.M., Gay, C.V. & Welch, D.R. The skeleton as a unique environment for breast cancer cells. Clin. Exp. Metastasis 20, 275-284 (2003).
42. Schneider, J.G., Amend, S.R. & Weilbaecher, K.N. Integrins and bone metastasis: integrating tumor cell and stromal cell interactions. Bone 48, 54-65 (2011).
43. Patel, L.R., Camacho, D.F., Shiozawa, Y., Pienta, K.J. & Taichman, R.S. Mechanisms of cancer cell metastasis to the bone: A multistep process. Future Oncol. 7, 1285-1297 (2011).
44. Moreau, J.E. et al. Tissue-engineered bone serves as a target for metastasis of human breast cancer in a mouse model. Cancer Res. 67, 10304-10308 (2007).
45. Taichman, R.S. Blood and bone: Two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 105, 2631-2639 (2005).
46. Kaplan, R.N. et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438, 820-827 (2005).
47. Shiozawa, Y. et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J. Clin. Invest. 121, 1298-1312 (2011).
48. Sacchetti, B. et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131, 324-336 (2007).
49. Muerza-Cascante, M.L., Haylock, D., Hutmacher, D.W. & Dalton, P.D. Melt electrospinning and its technologization in tissue engineering. Tissue Eng. Part B Rev. 21, 187-202 (2015).
50. Song, J. et al. An in vivo model to study and manipulate the hematopoietic stem cell niche. Blood 115, 2592-2600 (2010).
51. Yoshino, H. et al. Natural killer cell depletion by anti-Asialo GM1 antiserum treatment enhances human hematopoietic stem cell engraftment in NOD/Shi-scid mice. Bone Marrow Transplant. 26, 1211-1216 (2000).
52. Ishikawa, F. et al. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood 106, 1565-1573 (2005).
53. Ito, R., Takahashi, T., Katano, I. & Ito, M. Current advances in humanized mouse models. Cell. Mol. Immunol. 9, 208-214 (2012).
54. Macchiarini, F., Manz, M.G., Palucka, A.K. & Shultz, L.D. Humanized mice: Are we there yet? J. Exp. Med. 202, 1307-1311 (2005).
55. Lee, J. et al. Implantable microenvironments to attract hematopoietic stem/cancer cells. Proc. Natl. Acad. Sci. USA 109, 19638-19643 (2012).
56. Groen, R.W. et al. Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma. Blood 120, e9-e16 (2012).
57. Chen, Y. et al. Human extramedullary bone marrow in mice: A novel in vivo model of genetically controlled hematopoietic microenvironment. Blood 119, 4971-4980 (2012).
58. Holzapfel, B.M., Wagner, F., Thibaudeau, L., Levesque, J.P. & Hutmacher, D.W. Concise review: humanized models of tumor immunology in the 21st century: convergence of cancer research and tissue engineering. Stem Cells 33, 1696-1704 (2015).
59. Thibaudeau, L. et al. Mimicking breast cancer-induced bone metastasis in vivo: current transplantation models and advanced humanized strategies. Cancer Metastasis Rev. 33, 721-735 (2014).
60. Bersani, F. et al. Bioengineered implantable scaffolds as a tool to study stromal-derived factors in metastatic cancer models. Cancer Res. 74, 7229-7238 (2014).
61. Schuster, J., Zhang, J. & Longo, M. A novel human osteoblast-derived severe combined immunodeficiency mouse model of bone metastasis. J. Neurosurg. Spine 4, 388-391 (2006).
62. Seib, F.P., Berry, J.E., Shiozawa, Y., Taichman, R.S. & Kaplan, D.L. Tissue engineering a surrogate niche for metastatic cancer cells. Biomaterials 51, 313-319 (2015).
63. Goldstein, R.H., Reagan, M.R., Anderson, K., Kaplan, D.L. & Rosenblatt, M. Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis. Cancer Res. 70, 10044-10050 (2010).
64. Battula, V.L. et al. Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment. Blood 122, 357-366 (2013).
65. Azarin, S.M. et al. In vivo capture and label-free detection of early metastatic cells. Nat. Commun. 6, 8094 (2015).
66. Dondossola, E. et al. Abstract 4941: A humanized bone model for preclinical monitoring of prostate cancer lesions by intravital multiphoton microscopy. Cancer Res. 74, 4941 (2014).
67. Hughes, C.S., Postovit, L.M. & Lajoie, G.A. Matrigel: A complex protein mixture required for optimal growth of cell culture. Proteomics 10, 1886-1890 (2010).
68. Vukicevic, S. et al. Identification of multiple active growth factors in basement membrane Matrigel suggests caution in interpretation of cellular activity related to extracellular matrix components. Exp. Cell Res. 202, 1-8 (1992).
69. Thibaudeau, L., Holzapfel, B.M. & Hutmacher, D.W. Humanized mice models for primary bone tumor and bone metastasis research. Cell Cycle 14, 2191-2192 (2015).
70. Holzapfel, B.M. et al. Humanised xenograft models of bone metastasis revisited: novel insights into species-specific mechanisms of cancer cell osteotropism. Cancer Metastasis Rev. 32, 129-145 (2013).
71. Thibaudeau, L. et al. New mechanistic insights of integrin β1 in breast cancer bone colonization. Oncotarget 6, 332-344 (2015).
72. Wagner, F. et al. A validated preclinical animal model for primary bone tumor research. J. Bone Joint Surg. Am. 98, 916-925 (2016).
73. Kuznetsov, S.A. et al. Age-dependent demise of GNAS-mutated skeletal stem cells and normalization of fibrous dysplasia of bone. J. Bone Miner. Res. 23, 1731-1740 (2008).
74. Morrison, S.J. & Scadden, D.T. The bone marrow niche for haematopoietic stem cells. Nature 505, 327-334 (2014).
75. Heike, Y., Ohira, T., Takahashi, M. & Saijo, N. Long-Term human hematopoiesis in SCID-hu mice bearing transplanted fragments of adult bone and bone marrow cells. Blood 86, 524-530 (1995).
76. Hubin, F. et al. Maintenance of functional human cancellous bone and human hematopoiesis in NOD/SCID mice. Cell Transplant. 13, 823-831 (2004).
77. Miura, Y. et al. Mesenchymal stem cell-organized bone marrow elements: An alternative hematopoietic progenitor resource. Stem Cells 24, 2428-2436 (2006).
78. Meyer, L.H. & Debatin, K.M. Diversity of human leukemia xenograft mouse models: implications for disease biology. Cancer Res. 71, 7141-7144 (2011).
79. Manz, M.G. Human-hemato-lymphoid-system mice: opportunities and challenges. Immunity 26, 537-541 (2007).
80. Wunderlich, M. et al. AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3. Leukemia 24, 1785-1788 (2010).
81. Reinisch, A. et al. A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells. Nat. Med. 22, 812-821 (2016).
82. Reichert, J.C. et al. Mineralized human primary osteoblast matrices as a model system to analyse interactions of prostate cancer cells with the bone microenvironment. Biomaterials 31, 7928-7936 (2010).
83. Taubenberger, A.V., Quent, V.M., Thibaudeau, L., Clements, J.A. & Hutmacher, D.W. Delineating breast cancer cell interactions with engineered bone microenvironments. J. Bone Miner. Res. 28, 1399-1411 (2013).
84. Ding, L., Saunders, T.L., Enikolopov, G. & Morrison, S.J. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481, 457-462 (2012).
85. Raymaekers, K., Stegen, S., van Gastel, N. & Carmeliet, G. The vasculature: A vessel for bone metastasis. Bonekey Rep. 4, 742 (2015).
86. Yardeni, T., Eckhaus, M., Morris, H.D., Huizing, M. & Hoogstraten-Miller, S. Retro-orbital injections in mice. Lab Anim. 40, 155-160 (2011).
87. Scepansky, E., Goldstein, R. & Rosenblatt, M. Preclinical orthotopic and intracardiac injection models of human breast cancer metastasis to bone and their use in drug discovery. Curr. Protoc. Pharmacol. 52, 14.18 (2011).
88. Park, S.I., Kim, S.J., McCauley, L.K. & Gallick, G.E. Pre-clinical mouse models of human prostate cancer and their utility in drug discovery. Curr. Protoc. Pharmacol. 51, 14.15 (2010).
89. Campbell, J.P., Merkel, A.R., Masood-Campbell, S.K., Elefteriou, F. & Sterling, J.A. Models of bone metastasis. J. Vis. Exp (67), e4260 (2012).
90. Barbier, V., Winkler, I.G. & Levesque, J.P. Mobilization of hematopoietic stem cells by depleting bone marrow macrophages. Methods Mol. Biol. 904, 117-138 (2012).