Tumor spheroid-based and microtumor-based vascularized models for replicating the vascularized tumor microenvironment

Abstract

Background Tumor vasculature is a crucial pathway for supplying nutrients and oxygen to tumors during their progression, as well as facilitating the delivery of anticancer drugs or immunotherapeutic agents. Microfluidic technology has emerged as a powerful tool in creating microenvironments within 3-dimensional cell cultures that more closely resemble in vivo conditions, by enabling precise control of fluid flow. As a result, microfluidic devices have made significant progress in replicating both the structural and functional characteristics of the tumor microenvironment in vitro. Methods and Results In this study, we present two approaches for reconstructing the tumor vasculature using tumor spheroids or microtumors, with a particular focus on in vivo functional mimicry and experimental reproducibility. Tumor spheroid-based vascular models provide an observatory window into tumor vasculature centered on tumor spheroids, enabling quantitative measurement of the degree of abnormality of blood vessels developing around the tumor spheroid and the invasiveness of metastatic tumors. Microtumor-based vascular models, on the other hand, have the potential to enhance our comprehension of advanced and metastatic cancers at the single-cell level by elucidating the proliferative and metastatic capacities of tumor cells, as well as the vascular permeability that is contingent upon the subtypes of tumor cells. Conclusion Our platforms provide valuable insights into the development of novel in vitro models for studying the tumor microenvironment and advancing our understanding of cancer biology.

Keywords

• disease modeling
• microphysiological systems
• tumor microenvironment
• vascularization