Recent advances in organotypic tissue slice cultures for anticancer drug development

Abstract

Organotypic tissue slice culture is established from animal or patient tissues and cultivated in an in vitro ecosystem. This technique has made countless contributions to anticancer drug development due to the vast number of advantages, such as the preservation of the cell repertoire and immune components, identification of invasive ability of tumors, toxicity determination of compounds, quick assessment of therapeutic efficacy, and high predictive performance of drug responses. Importantly, it serves as a reliable tool to stratify therapeutic responders from nonresponders and select the optimal standard-ofcare treatment regimens for personalized medicine, which is expected to become a potent platform and even the gold standard for anticancer drug screening of individualization in the near future.

GITR and TIGIT immunotherapy provokes divergent multi-cellular responses in the tumor microenvironment of gastrointestinal cancers

“…We confirmed that the TSCs cultured for 24 hours maintained the cellular characteristics similar to the baseline state of the TME (i.e., T0 cell conditions at time of resection). As noted previously, other groups have used short culture periods to maintain the cellular diversity found in the native TME (4–7). First, we evaluated the TSC cellularity using hematoxylin and eosin ( H&E ) staining of the cultures.…”

“…The copyright holder for this preprint this version posted March 15, 2023. ; https://doi.org/10.1101/2023.03. 13.532299 doi: bioRxiv preprint tumor (4)(5)(6)(7). While TSCs have been used to evaluate the effects of chemotherapy agents in primary tumors specimens (8)(9)(10), only a limited number of recent studies have leveraged them to determine the consequences of immunotherapies such as anti-PD-1, anti-TIM-3, anti-IL-10 and CAR-T cells (11,12).…”

“…The tissue sections' thickness is in the range of several hundred microns which enables rapid diffusion of media, oxygen and other molecules. This primary tissue culture approach has been well-established in preserving the cellular TME of original tumor (4)(5)(6)(7). While TSCs have been used to evaluate the effects of chemotherapy agents in primary tumors specimens (8)(9)(10), only a limited number of recent studies have leveraged them to determine the consequences of immunotherapies such as anti-PD-1, anti-TIM-3, anti-IL-10 and CAR-T cells (11,12).…”

Complex in vitro model: A transformative model in drug development and precision medicine

“…The tissue slice culture prototype was first proposed by Dr. Harford's team and involved cutting the tissue into small pieces 42 . These tissue slices can be separated directly from normal organs and tumor tissues from humans and animals, providing the natural advantage of maintaining complex structural features and microenvironments in vitro 43 . However, tissue slices cannot be maintained under long‐term culture or expansion in vitro, with the culture period typically lasting 1 to 2 weeks only 44 .…”

Mapping Extracellular Space Features of Viral Encephalitis to Evaluate the Proficiency of Anti‐Viral Drugs

“…While cell culture models can evaluate drugs quickly and inexpensively, they cannot fully replicate the in vivo environment. [ 4 ] Animal models can more accurately mimic the infection process, but they are time‐consuming and costly to conduct, making them more challenging. [ 5 ] Therefore, there is a need to develop rapid assessment methods that can accurately predict the efficacy of antiviral drugs in the brain and provide a reliable basis for their clinical translation.…”