New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay

Several other tumor chips have been developed, encompassing features such as tumor vasculature, stromal cells, or immune cells, and offering advantages in terms of rapid fabrication, reproducibility, real-time imaging and analysis, capturing tumor type and heterogeneity, facilitating robust drug testing, target discovery and personalized therapy screenings, and enabling multicellular crosstalk.

“Besides this model, several other tumor chips have been developed, encompassing features such as tumor vasculature (Yu et al. (2019); Wan et al. (2023); Nashimoto et al. (2020); Neufeld et al. (2021); Kim et al. (2022); Mannino et al. (2017); Shirure et al. (2018), stromal cells (Yu et al. (2019); Ibrahim et al. (2022); Karakas et al. (2017), or immune cells (Surendran et al. (2021); Aung et al. (”

In ovarian cancer MPS, a microfluidic device with three parallel channels using ECs, fibroblasts, SKOV3, OV90 spheroids, and CAR T cells showed a high level of tumor vascularization and recruitment of CAR T cells.

“| Ovarian | Wan et al. (2023) | Microfluidic device with three parallel channels | ECs, fibroblasts, SKOV3, OV90 spheroids, CAR T cells | High level of tumor vascularization and recruitment of CAR T cells |”

Wan et al. developed a tumor spheroid model that allows high tumor vascularization via a living vasculature network and elucidation of the role of fibroblasts within the tumor microenvironment.

“In an approach to improve tumor architecture, promote tumor-stromal interactions and promote tumor vascularization, Wan and colleagues developed a tumor spheroid model that allows for high levels of tumor vascularization via a living vasculature network and further allows elucidation of the role of fibroblasts within the TME (Wan et al., 2023).”

The sequential spheroid result is indicative of complex microenvironmental remodeling and enhanced angiogenesis typical of in vivo vascularized tumors.

“Interestingly, the tumor spheroids formed by the sequential approach led to the highest level of tumor vascularization, vessel perfusability and fibroblast area, which is indicative of complex microenvironmental remodeling processes and enhanced angiogenesis that typically occurs in in vivo vascularized tumors (Wan et al., 2023).”

Tumor spheroids formed by sequential addition of fibroblasts to pre-formed tumor spheroids led to the highest level of tumor vascularization, vessel perfusability, and fibroblast area.

“Interestingly, the tumor spheroids formed by the sequential approach led to the highest level of tumor vascularization, vessel perfusability and fibroblast area, which is indicative of complex microenvironmental remodeling processes and enhanced angiogenesis that typically occurs in in vivo vascularized tumors (Wan et al., 2023).”

CAR T cells were recruited to tumor spheroids, extravasated from tumor vessels, interacted with tumor cells, and led to a strong IFN-γ response and higher density of dead cells in the tumor region.

“Interestingly, CAR T cells were recruited to the tumor spheroids, extravasated from the tumor vessels and engaged in interactions with tumor cells; leading to a strong IFN-γ response and a higher density of dead cells in the tumor region (Wan et al., 2023).”