New Advances in the Study of Bone Tumors: A Lesson From the 3D Environment

Abstract

Bone primary tumors, such as osteosarcoma, are highly aggressive pediatric tumors that in 30% of the cases develop lung metastasis and are characterized by poor prognosis. Bone is also the third most common metastatic site in patients with advanced cancer and once tumor cells become homed to the skeleton, the disease is usually considered incurable, and treatment is only palliative. Bone sarcoma and bone metastasis share the same tissue microenvironment and niches. 3D cultures represent a new promising approach for the study of interactions between tumor cells and other cellular or acellular components of the tumor microenvironment (i.e., fibroblasts, mesenchymal stem cells, bone ECM). Indeed, 3D models can mimic physiological interactions that are crucial to modulate response to soluble paracrine factors, tumor drug resistance and aggressiveness and, in all, these innovative models might be able of bypassing the use of animal-based preclinical cancer models. To date, both static and dynamic 3D cell culture models have been shown to be particularly suited for screening of anticancer agents and might provide accurate information, translating in vitro cell cultures into precision medicine. In this mini-review, we will summarize the current state-of-the-art in the field of bone tumors, both primary and metastatic, illustrating the different methods and techniques employed to realize 3D cell culture systems and new results achieved in a field that paves the way toward personalized medicine.

The Microfluidic Trainer: Design, Fabrication and Validation of a Tool for Testing and Improving Manual Skills

“…Similarly, in our lab, we recently approached microfluidic devices for the in vitro modelling of bone physiology and disease [ 13 ]. In contrast to the advantages of using such devices, there are some technical difficulties in the practical application of this technology.…”

“…The main advantages of a microfluidic devices in in vitro disease modelling are: (1) working at a single-cell scale [ 9 , 10 ]; (2) the use of techniques that take into account 3D architecture and chemical/physical microenvironment composition of the referred tissue that cannot be considered in 2D monolayer cell culture [ 11 , 12 , 13 , 14 ]; (3) a high level of standardization and reproducibility; (4) a low-budget production [ 15 ]; (5) maximization of the information collected starting from small samples, thereby reducing the costs for the experimentation, as compared to conventional benchtop equipment [ 15 ]. Miniaturization and cost-cutting for the operator that works in the biomedical field also allow enhancing the scalability and increasing the number of replicates that can be performed in a single assay.…”

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis

“…The stroma of these tumors comprises osteoblasts, osteoclasts, endothelial and immune cells and mesenchymal stem cells. In particular, osteoclast have grabbed great attention because their activity (bone destruction) can be metabolically enhanced directly by tumor cells and, reversibly, the presence of osteoclasts boosts the aggressiveness of cancer cells [91].…”

Trends in Bone Metastasis Modeling

“…However, not all cell lines form spheroids; some arrange in irregular cell aggregates. Moreover, spheroids can be considered too simplistic and not appropriate to simulate all the cell-cell and cell-ECM interactions that can affect the efficacy of anti-cancer drugs [94]. Moving the model to a fully embedded system offers further opportunities to mimic a tumor environment facilitating physiological cellular interactions, metabolism, growth, and metastatic invasion.…”