Table 1. 3D device-assisted assembly models of bone metastasis.
| 3D model | Cancer cell type | Experimental design | Main results | Advantages | Disadvantages | Reference |
|---|---|---|---|---|---|---|
| Rotating wall vessel (RWV) bioreactor | Prostate cancer cells | Co-culture of human osteosarcoma cell line, normal immortalized human osteoblastic cell line with LN and C4-2 prostate cancer cells and derivate bone stromal cells. | Normal and osteosarcoma bone stromal fibroblast co-cultured with C4-2 underwent permanent morphological changes. | - Forges direct interaction between prostate cancer cells and bone stromal cells; - Easily reproducible. |
- Absent 3D matrix interaction; - No similarities with native bone microenvironments; - No hypoxic setting. |
Sung et al.2008 |
| Bioreactor system | Breast cancer cells | Co-culture of murine derived OT with MDA-MB-231 metastatic breast cancer cells. | MDA-MB-231 breast cancer cells form colonies which were able to penetrate the murine OT. | - Murine OT generated from bioreactor showed bone tissue like characteristics; - Able to detect cell migration and matrix remodeling. |
- Difficult to separate the different cell types; - 3D cultures grow for several months; - No hypoxic setting; - Difficult to reproduce. |
Dhurjati et al 2008; Mastro et al. 2009; Krishnan et al. 2011 |
| Bioreactor system | Breast cancer cells | Co-culture of mineralized collagenous osteoblastic tissue with osteoclasts followed by reinfusion with proliferating pre-osteoblasts and MDA-MB-231 breast cancer cells. | Osteoclasts, differentiated in the presence of osteoblasts, led to degradation of the collagen-rich extracellular matrix. Addition of metastatic breast cancer cells to the co-culture mimicked the vicious cycle. | - Detection of cell migration and matrix remodeling. | - Difficult to separate the different cell types; - 3D cultures grow for several months; - No hypoxic setting; - Difficult to reproduce. |
Krishnan et al. 2014 |
| Bioreactor system | Melanoma cells, human prostate cells and mouse myeloma | Co-cultures of mouse melanoma cells, human prostate cells and mouse myeloma cells with MC3T3-E1 osteoblasts. | Each of these different lines displayed characteristic growth patterns. | - Detection of cell migration and matrix remodeling. | - Difficult to separate to different cell types; - 3D cultures grow for several months; - No hypoxic setting; - Difficult to reproduce. |
Krishnan et al. 2015 |
| Microfluid system | Breast cancer cells | Tri-culture of osteodifferentiated hBM-MSCs, HUVECs and MDA-MB-231 breast cancer cells. | The model allows to quantify tumor cell extravasation and micrometastasis generation within a bone-like microenvironment. | - Biochemically and biophysically controlled 3D microenvironments. | - Vascular wall represented by an endothelial monolayer; - Difficult to separate different cell types; - No similarities with native bone microenvironments; - Absent 3D cell-matrix interaction; - No hypoxic setting; - Difficult to reproduce. |
Bersini et al. 2014 |
| Microfluid system | Breast cancer cells | Model created to study MDA-MB-231 breast cancer cell extravasation into an actively secreting bone mimicking microenvironment generated with osteo-differentiated hBM-MSCs through perfusable human microvascular networks composed of endothelial and mural-like cells. | The model demonstrated its effectiveness as a drug screening assay, being able to investigate the antimetastatic role of adenosine in a human bone-mimicking microenvironment. | - Presence of a microvascular network; - Analysis of cell attachment under more relevant dynamic conditions. |
- Difficult to separate to different cell types; - No similarities with native bone microenvironments; - Absent 3D cell-matrix interaction; - No hypoxic setting; - Difficult to reproduce. |
Jeon et al. 2015 |
| Microfluid system | Prostate cancer cells | Tri-culture of PC-3 prostate cancer cells, osteoblasts (MC3T3-E1) and HUVECs. | Formation of uniformly-sized spheroids in co-culture. | - Biochemically and biophysically controlled 3D microenvironments. | - Difficult to separate to different cell types; - No similarities to the native bone microenvironments; - Absent 3D cell-matrix interaction; - No hypoxic setting; - Difficult to reproduce. |
Hsiao et al. 2009 |