Development of Lung-on-Chip Devices for Modeling Pulmonary Metastasis of Osteosarcoma
Overall survival for metastatic osteosarcoma (OS) is dismal at less than 20% with no new advancements in therapy over the past several decades. The most common site of OS metastasis is in the lungs. It is hypothesized that the resistance of pulmonary metastasis to currently available treatment is in part due to the “protective” role the lung microenvironment has on metastatic cells. It is also well recognized by the OS community that targeting (micro)metastasis and its progression, i.e. tumor lesions undetectable in clinic, can be critical in terms of breaking the survival plateau of OS patients observed over the past few decades. Therefore, a predictive model that can capture the complex interactions between cancer cells and their physicochemical microenvironment in vivo can be critical for drug and chemotherapeutic strategy development. 2D and even 3D spheroid cell cultures have been used, but are not adequate in this aspect. Likewise, animal models can be expensive and may fail to recapitulate the human condition. Recently, microfluidic engineered organ-on-chip models have emerged as promising humanized in vitro platforms for drug screening while mimicking unique tissue structures in 3D. In this project, we demonstrate our progress in building organ-on-chip devices that model the lung for study of OS metastasis. Two models of our “Lung-on-chip” are presented: the first focuses on conditioning OS spheroid growth media, and the second implements a hydrogel model of pulmonary interstitial space. To model OS, we use the SJSA-1 cell line cultured in non-adhering spheroid forming 96 well plates to mimic the spheroidal properties of micro lesions that go undetected in clinic. We present data that describe the viability of these cancerous spheroids with incubation time and initial cell seed quantities. With these models, we hope to mimic the lung microenvironment and therefore provide a viable platform to aid in the development of metastatic OS treatment.