Abstract
Currently, research on intestinal diseases is mainly based on animal models and cell lines in monolayers. However, these models have drawbacks that limit scientific advances in this field. Three-dimensional (3D) culture systems named organoids are emerging as a reliable research tool for recapitulating the human intestinal epithelium and represent a unique platform for patient-specific drug testing. Intestinal organoids (IOs) are crypt–villus structures that can be derived from adult intestinal stem cells (ISCs), embryonic stem cells (ESCs), or induced pluripotent stem cells (iPSCs) and have the potential to serve as a platform for individualized medicine and research. However, this emerging field has not been bibliometric summarized to date. Here, we performed a bibliometric analysis of the Web of Science Core Collection (WoSCC) database to evaluate 5,379 publications concerning the use of organoids; the studies were divided into four clusters associated with the current situation and future directions for the application of IOs. Based on the results of our bibliometric analysis of IO applications, we systematically summarized the latest advances and analyzed the limitations and prospects.
Highlights
Recent progressive improvements in personalized medicine as a result of substantial developments in molecular biology and genetic research indicate the need for preclinical studies
Intestinal organoids (IOs) recapitulate intestinal epithelial structures in vivo: single leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) + intestinal stem cells (ISCs) initially form villus-like spherical structures with a closed-loop hollow lumen, and the cyst buds up, differentiates into a crypt-like structure, and forms a mature organoid structure; subsequently, ISCs stay at the bottom of the budding domains, while other differentiated intestinal epithelial cells (IECs) migrate to the central cyst (Sato et al, 2009; Date and Sato, 2015)
Methods have been developed to culture CRC organoids originating from both surgery specimens and endoscopic biopsy tissues
Summary
Recent progressive improvements in personalized medicine as a result of substantial developments in molecular biology and genetic research indicate the need for preclinical studies. Cell lines grown in monolayers, patient-derived tumor xenografts (PDTXs), and genetically engineered mouse models (GEMMs) are commonly used in experimental research. Most of these models fail to phenocopy the response of diseases and drugs directly (see Table 1); human cell lines originate from a single type of cancer or embryonic cells due to strong selection bias (e.g., normal epithelium-derived cell lines are immortalized by virus transformation), which cannot recreate complex cell–cell interactions, heterogeneous environments, and gene mutations or chromosomal abnormalities (Bein et al, 2018; Fujii and Sato, 2021); the associated costs, animal ethics, and species differences between experimental animals and humans are major issues that must be resolved (Sato and Clevers, 2013; Hickman et al, 2014; Liu et al, 2016; Bein et al, 2018; Kapalczynska et al, 2018; Pereira et al, 2018; Yin et al, 2019). Identifying simpler, more robust, and widely available preclinical models for basic gastrointestinal research has rapidly become a subject of interest in recent decades
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