Applications of human organoids in the personalized treatment for digestive diseases

Abstract

Digestive system diseases arise primarily through the interplay of genetic and environmental influences; there is an urgent need in elucidating the pathogenic mechanisms of these diseases and deploy personalized treatments. Traditional and long-established model systems rarely reproduce either tissue complexity or human physiology faithfully; these shortcomings underscore the need for better models. Organoids represent a promising research model, helping us gain a more profound understanding of the digestive organs; this model can also be used to provide patients with precise and individualized treatment and to build rapid in vitro test models for drug screening or gene/cell therapy, linking basic research with clinical treatment. Over the past few decades, the use of organoids has led to an advanced understanding of the composition of each digestive organ and has facilitated disease modeling, chemotherapy dose prediction, CRISPR-Cas9 genetic intervention, high-throughput drug screening, and identification of SARS-CoV-2 targets, pathogenic infection. However, the existing organoids of the digestive system mainly include the epithelial system. In order to reveal the pathogenic mechanism of digestive diseases, it is necessary to establish a completer and more physiological organoid model. Combining organoids and advanced techniques to test individualized treatments of different formulations is a promising approach that requires further exploration. This review highlights the advancements in the field of organoid technology from the perspectives of disease modeling and personalized therapy.

Emerging therapeutic drug monitoring technologies: considerations and opportunities in precision medicine

“…However, strategies such as incorporating the use of patient-derived organoids to perform drug screening, dose optimization, and treatment holds promise for improving patient outcomes ( Bose et al, 2021 ). Patient-derived organoids capture important patient-specific features, including the patient’s physiology and tissue microenvironments, and is being explored for the treatment of different cancers ( Zhou et al, 2021 ; Shin et al, 2023 ; Schmäche et al, 2024 ), including assessing cancer drug resistance ( Sun et al, 2024 ), and digestive disorders ( Wang et al, 2022 ), to name a few. Integrating this approach with patient-focused N-of-1 trials will help to identify, handle, and mitigate issues associated with using population-based data.…”

Organoids: The current status and biomedical applications

“…Targeted therapy is a part of precision medicine that uses specific compounds to inhibit specific molecular markers or signaling pathways of tumors or other diseases. Organoids are also used to perform target drug screening and discover potential therapeutic targets owing to the important roles of organoids in target therapy theories 100,266 . Ovarian tumor organoids derived from patients with three tumor types had been used as a high‐throughput screening platform to test the sensitivity to 240 protein kinase inhibitors by Phan et al., 267 and this platform allowed rapidly obtaining drug sensitivity results for ovarian cancers.…”

“…The main components of the medium for the submerged culture include adDMEM/F12, penicillin/streptomycin, GlutaMAX, HEPES, B27, epidermal growth factor (EGF), FGF2, FGF10, Wnt3A, Noggin, R‐spodin‐1, Prostaglandin E2, N‐Acetylcysteine, Nicotinamide, Y27632, A‐8301, and SB202190 37,99 . The medium composition varies when forming organoids from different tissues, and which specific factors need to be added or removed usually depends on the requirements of the tissue from which they originate for the corresponding signal or hormone 100 …”

“…Organoids are also used to perform target drug screening and discover potential therapeutic targets owing to the important roles of organoids in target therapy theories. 100,266 Ovarian tumor organoids derived from patients with three tumor types had been used as a high-throughput screening platform to test the sensitivity to 240 protein kinase inhibitors by Phan et al, 267 and this platform allowed rapidly obtaining drug sensitivity results for ovarian cancers. Yuan et al 32 screened 20 US FDA-approved targeted drugs with low toxicity to normal gallbladder organoids and found that HDAC inhibitors could significantly decrease the growth of the gallbladder tumoroids.…”

“… 37 , 99 The medium composition varies when forming organoids from different tissues, and which specific factors need to be added or removed usually depends on the requirements of the tissue from which they originate for the corresponding signal or hormone. 100 …”