A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Quent, Verena M.C.; Taubenberger, Anna; Reichert, Johannes C.; Martine, Laure; Clements, Judith A.; Hutmacher, Dietmar W.; Loessner, Daniela

doi:10.1002/term.2517

Cited by 22 publications

(15 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous doses of BMP7 delivered with a fibrin hydrogel ranged from 10 to 30 g (10,14,19) and 20 to 30 g in the case of BMP2 (6,12). These are rather large doses of BMP when considering the desired controlled release of lower doses for bone regeneration (38,39) yet commonly required in the field of ectopic bone formation (6,10,12,14,19). Since, in the present study, we delivered a 20-g BMP2 dose at an orthotopic location (i.e., mouse femur), future studies should explore the dose impact on the remodeling at the host bone/ossicle junction.…”

Section: Discussionmentioning

confidence: 99%

Human and mouse bones physiologically integrate in a humanized mouse model while maintaining species-specific ultrastructure

et al. 2020

View full text Add to dashboard Cite

Humanized mouse models are increasingly studied to recapitulate human-like bone physiology. While human and mouse bone architectures differ in multiple scales, the extent to which chimeric human-mouse bone physiologically interacts and structurally integrates remains unknown. Here, we identify that humanized bone is formed by a mosaic of human and mouse collagen, structurally integrated within the same bone organ, as shown by immunohistochemistry. Combining this with materials science techniques, we investigate the extracellular matrix of specific human and mouse collagen regions. We show that human-like osteocyte lacunar-canalicular network is retained within human collagen regions and is distinct to that of mouse tissue. This multiscale analysis shows that human and mouse tissues physiologically integrate into a single, functional bone tissue while maintaining their species-specific ultrastructural differences. These results offer an original method to validate and advance tissue-engineered human-like bone in chimeric animal models, which grow to be eloquent tools in biomedical research.

show abstract

Section: Discussionmentioning

confidence: 99%

Human and mouse bones physiologically integrate in a humanized mouse model while maintaining species-specific ultrastructure

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In a humanised system, silk scaffolds seeded with BMSCs supported the metastatic spread of SUM1315 human breast cancer cells from the orthotopic implantation site in the murine mammary fat pad ( Moreau et al, 2007 ). Moreover, a humanised bone model generated by solution-electrospun CaP-PCL scaffolds and human osteoblasts supported the metastatic growth of different human breast cancer cell lines (MDA-MB-231, SUM1315 and MDA-MB-231BO) and osteolytic damage caused by the breast cancer cells could be observed in the TE bone construct ( Quent et al, 2018 ). In the same TE bone model, Hesami et al described osteoclast-mediated destruction of the bone environment following direct injection of LNCaP and PC3 prostate cancer cells into the TEC ( Hesami et al, 2014 ).…”

Section: Humanised Bone Approaches For Disease Modellingmentioning

confidence: 99%

Animal models for bone tissue engineering and modelling disease

McGovern

Griffin

Hutmacher

2018

Disease Models &Amp; Mechanisms

224

172

View full text Add to dashboard Cite

Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches.

show abstract

“…Other novel humanized bone models utilize different kinds of bone scaffolds. A bone scaffold enables normal bone formation (humanized bone) in mice, and injection of breast cancer cells produced a bone metastasis model similar to metastasis in humans [45]. In a model established by Holzapfel and colleagues [46], mice are implanted with biodegradable tubular composite scaffolds together with mesenchymal progenitor cells synthetizing bone [46].…”

Section: Other Models Related To Bone Metastasismentioning

confidence: 99%

Novel and Conventional Preclinical Models to Investigate Bone Metastasis

et al. 2019

View full text Add to dashboard Cite

Purpose of Review The purpose of this review is to emphasize the use of bone metastasis models in preclinical research. As classical models have been thoroughly discussed in recent reviews, we here highlight the most important aspects from these papers with a special focus on novel models developed during the past 5 years. Recent Findings Preclinical mouse models to study bone metastasis can be divided by cancer cell inoculation techniques (spontaneous, systemic, or local) or by immunological background of the mice (immunodeficient, syngeneic, or humanized). Additionally, novel computational, in vitro co-culture, and humanized bone models have been established. Summary Various models can be used to approach distinct research questions. Understanding limitations of the models is essential when planning a study and interpreting the results. Development of novel models will increase understanding of the complex biology and advance the discovery of new therapies targeting bone metastases.

show abstract

A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Cited by 22 publications

References 40 publications

Human and mouse bones physiologically integrate in a humanized mouse model while maintaining species-specific ultrastructure

Human and mouse bones physiologically integrate in a humanized mouse model while maintaining species-specific ultrastructure

Animal models for bone tissue engineering and modelling disease

Novel and Conventional Preclinical Models to Investigate Bone Metastasis

Contact Info

Product

Resources

About