Bridging the gap: the role of 3D cell cultures in mimicking tumor microenvironment for enhanced drug testing accuracy

Abstract

Cell culture is a crucial technology in life science research, particularly in cancer studies. The morphology and biological properties of tumor cells, along with the mechanisms of tumor development, are highly dependent on their culture conditions. Antitumor drug sensitivity testing is essential for cancer treatment, helping to identify effective therapies and reduce patient treatment burden. Currently, 2D cell culture remains the primary method for antitumor drug sensitivity testing due to its cost-effectiveness, ease of operation, and high-throughput screening capability. However, it does not accurately replicate the tumor microenvironment. Animal models are important tools for drug development, but they are not suitable for high-throughput screening. Recent advancements in 3D culture technologies have addressed this limitation. These technologies can better mimic the tumor microenvironment and can accurately reflect tumor biological behavior, gene expression, and signaling pathways. This paper summarizes the current in vitro and in vivo culture models, discusses emerging three-dimensional cell culture technologies, and highlights their ability to effectively simulate the tumor microenvironment and their significant potential in drug sensitivity testing.

Keywords: 3D cell culture; drug screening; drug sensitivity testing; organoids; tumor microenvironment.

FIGURE 1

Overview of cell culture technology.

FIGURE 2

Comparison of 3D-ACM and 3D-FBS culture. The culture medium used for autologous culture is usually derived from patient serum or body fluids such as hydrothorax and ascite, while the traditional method used FBS for culture.

FIGURE 3

Organotypic tissue slice culture method. Normal or tumor tissue is obtained from experimental animals or humans, cut into thin slices, and placed in a dish for culture. Floating slice culture is placed directly in a culture dish. Filter-supporting slice culture is first placed on a filter and then placed in a culture dish. 3D-TSC is first wrapped slice with collagen, then placed in the culture inserts, and finally placed in a culture dish.

FIGURE 4

Flow chart of humanized mouse construction. Establishment of a mouse model with a human immune system by introducing peripheral blood mononuclear cells or hematopoietic stem cells from umbilical cord blood into immunodeficient mice.