In vitro bone metastasis dwelling in a 3D bioengineered niche

Abstract

Bone is the most frequent metastasis site for breast cancer. As well as dramatically increasing disease burden, bone metastases are also an indicator of poor prognosis. One of the main challenges in investigating bone metastasis in breast cancer is engineering in vitro models that replicate the features of in vivo bone environments. Such in vitro models ideally enable the biology of the metastatic cells to mimic their in vivo behavior as closely as possible. Here, taking benefit of cutting edge technologies both in microfabrication and cancer cell biology, we have developed an in vitro breast cancer bone-metastasis model. To do so we first 3D printed a bone scaffold that reproduces the trabecular architecture and that can be conditioned with osteoblast-like cells, a collagen matrix, and mineralized calcium deposition. We thus demonstrated that this device offers an adequate soil to seed breast cancer bone metastatic cells. In particular, patient-derived xenografts being considered as better approach than cell lines to achieve clinically relevant results, we demonstrate the ability of this biomimetic bone niche model to host patientderived xenografted metastatic breast cancer cells. These patient-derived xenograft cells show a long term survival in the bone model and maintain their cycling propensity, and exhibit the same modulated drug response as in vivo. This experimental system enables access to the idiosyncratic features of the bone microenvironment and cancer bone metastasis, which has implications for drug testing.

Perspectives for 3D-Bioprinting in Modeling of Tumor Immune Evasion

“…Additionally, the transcriptomic pattern of response to doxorubicin and 5-fluorouracil differed between the cells cultured in 3D versus 2D. Han et al focused on metastatic disease, specifically estrogen-receptor-positive breast cancer metastases to bone tissue [84]. First, they fabricated an osteomimetic DS-3000 resin scaffold using stereolitography, which was subsequently seeded with patient-derived cells isolated from bone lesion biopsies.…”

Three-Dimensional (3D) Printing in Cancer Therapy and Diagnostics: Current Status and Future Perspectives

“…A 3D printed bone scaffold was developed and conditioned with osteoblast-like cells, collagen matrix, and calcium. This scaffold was then cultured with patient-derived metastatic breast cancer cells and the data showed an increased survival of cells in the bone model and modulated drug response [172]. The 3D scaffold was printed using E-jet 3D printing to mimic the tumor micro-environment and p53-deleted cancer cells were cultured on the 3D scaffolds.…”

Influence of Trabecular Geometry on Scaffold Mechanical Behavior and MG-63 Cell Viability

“…Additionally, customized dental impressions were manufactured in DS3000 to facilitate the visualization of margins preparation for fillings [ 18 ]. However, DS3000 manufactured by VPP was also used for 3D architectures with multidisciplinary potential applications, ranging from biomimetic scaffolds for cell culture to microfluidics [ 19 , 20 ]. Han et al [ 19 ] created an in vitro model of a bone metastasis microenvironment in DS3000, reproducing the trabecular architecture defined from X-ray micro-computed tomography scan images.…”