Holzapfel, Boris M. and Wagner, Ferdinand and Loessner, Daniela and Holzapfel, Nina P. and Thibaudeau, Laure and Crawford, Ross and Ling, Ming-Tat and Clements, Judith A. and Russell, Pamela J. and Hutmacher, Dietmar W. (2014) Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone. BIOMATERIALS, 35 (13). pp. 4108-4115. ISSN 0142-9612, 1878-5905
Full text not available from this repository. (Request a copy)Abstract
The development of effective therapeutic strategies against prostate cancer bone metastases has been impeded by the lack of adequate animal models that are able to recapitulate the biology of the disease in humans. Bioengineered approaches allow researchers to create sophisticated experimentally and physiologically relevant in vivo models to study interactions between cancer cells and their microenvironment under reproducible conditions. The aim of this study was to engineer a morphologically and functionally intact humanized organ bone which can serve as a homing site for human prostate cancer cells. Transplantation of biodegradable tubular composite scaffolds seeded with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone construct including a large number of human mesenchymal cells which were shown to be metabolically active and capable of producing extracellular matrix components. Micro-CT analysis demonstrated that the newly formed ossicle recapitulated the morphological features of a physiological organ bone with a trabecular network surrounded by a cortex-like outer structure. This microenvironment was supportive of the lodgement and maintenance of murine haematopoietic cell clusters, thus mimicking a functional organ bone. Bioluminescence imaging demonstrated that luciferase-transduced human PC3 cells reproducibly homed to the humanized tissue engineered bone constructs, proliferated, and developed macro-metastases. This model allows the analysis of interactions between human prostate cancer cells and a functional humanized bone organ within an immuno-incompetent murine host. The system can serve as a reproducible platform to study effects of therapeutics against prostate cancer bone metastases within a humanized microenvironment. Crown Copyright (c) 2014 Published by Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN BREAST-CANCER; CELL-LINE PC-3; MOUSE MODEL; ORTHOTOPIC IMPLANTATION; ZOLEDRONIC ACID; XENOGRAFT MODEL; MICE; ESTABLISHMENT; OSTEOTROPISM; EXPRESSION; Bone metastasis; Prostate cancer; Homing; Tissue engineering; Humanized bone; Osteotropism |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Orthopädie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Nov 2019 08:59 |
| Last Modified: | 15 Nov 2019 09:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10364 |
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