gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2013)

22.10. - 25.10.2013, Berlin

An in vivo humanised tissue-engineered prostate cancer bone tumour model

Meeting Abstract

  • presenting/speaker Parisa Hesami - Queensland University of Technology, Brisbane, Australia
  • Laura Gregory - Queensland University of Technology, Brisbane, Australia
  • Judith Clements - Queensland University of Technology, Brisbane, Australia
  • Dietmar Werner Hutmacher - Queensland University of Technology, Brisbane, Australia

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2013). Berlin, 22.-25.10.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocGR15-999

doi: 10.3205/13dkou513, urn:nbn:de:0183-13dkou5133

Published: October 23, 2013

© 2013 Hesami et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Prostate cancer (PCa) regularly forms bone metastases for which there is no effective treatment available. Several in vivo models have been developed to investigate PCa-bone interactions. The standard human bone chip model in mice is limited by tissue variability, low viability and poor vascularisation. We aimed to overcome these limitations by using human tissue-engineered bone constructs (hTEBCs), made from polymer scaffolds in conjunction with human primary osteoblasts (hOBs).

Methods: Polymer scaffolds seeded with human osteoblasts, and human bone chips were implanted into the dorsum of NOD/SCID mice. In the first group mice were euthanised after 7 and 12 weeks. In the second group human PCa cells (PC3 and LNCaP) were injected directly into the constructs 12 weeks post-implantation. Mice were euthanised 7 to 8 weeks post injection. Implants were then excised for micro-ct, histology, histochemistry and immunohistochemistry (IHC) analysis.

Results: Mineralised tissue volume from explanted hTEBCs at 12 weeks showed significant amount of bone formation (µ-ct). Hematoxylin and Eosin (H&E) and IHC analyses confirmed the high viability of the newly formed bone and further revealed the presence of bone marrow. On the contrary, bone chips had a significantly lower degree of viability and bone marrow was replaced with adipcytes and fibrous tissue as observed in the H&E staining. We found a 70-100% success rate of tumour formation in hTEBCs. Micro-ct and histology results for PC3 injected hTEBCs reflected the different characteristics of this cell line regarding the production of osteolytic lesions. Histochemistry (TRAP staining) revealed a significantly higher number of osteoclasts in PC3 formed tumours in hTEBCs. Macroscopically, PC3 tumours were light in colour while LNCaP tumours had a dark red appearance, indicating high vascularisation. H&E, CD31 (for new blood vessel formation) and VEGF (vascular endothelial growth factor) staining of paraffin sections verified the differences in PC3 and LNCaP tumours in terms of blood vessel formation (CD31), angiogenesis (VEGF) and tumour behaviour/aggressiveness (H&E) in hTEBC and bone chip microenvironment.

Conclusion: This study was successful demonstrating that hTEBC implanted into immunodeficient mice were able to produce a significant amount of the organ bone (all bone marrow populations were found inside the viable newly formed bone). Moreover, this model is efficient in forming tumours within the formed bone tissue, which makes it a highly reproducible in vivo model suitable to study PCa-bone interactions. PC3 tumours showed their pronounced osteolytic response. Higher number of immature leaky blood vessels (anti-CD31) as well as the large mature blood vessels (anti-vWF) in LNCaP tumours compared with PC3 tumours could explain the dark colour in haemorrhaged LNCaP tumours.