Int J Stem Cells.  2024 Nov;17(4):337-346. 10.15283/ijsc23075.

Gastric Organoid, a Promising Modeling for Gastric Stem Cell Homeostasis and Therapeutic Application

• Lee S
• Choi JH
• Park SY
• Kim J

• KMID: 2562354
• DOI: http://doi.org/10.15283/ijsc23075

Abstract

The elucidation of the pathophysiology underlying various diseases necessitates the development of research platforms that faithfully mimic in vivo conditions. Traditional model systems such as two-dimensional cell cultures and animal models have proven inadequate in capturing the complexities of human disease modeling. However, recent strides in organoid culture systems have opened up new avenues for comprehending gastric stem cell homeostasis and associated diseases, notably gastric cancer. Given the significance of gastric cancer, a thorough understanding of its pathophysiology and molecular underpinnings is imperative. To this end, the utilization of patient-derived organoid libraries emerges as a remarkable platform, as it faithfully mirrors patient-specific characteristics, including mutation profiles and drug sensitivities. Furthermore, genetic manipulation of gastric organoids facilitates the exploration of molecular mechanisms underlying gastric cancer development. This review provides a comprehensive overview of recent advancements in various adult stem cell-derived gastric organoid models and their diverse applications.

Keyword

Organoids; Stem cells; Homeostasis; Disease; Therapeutics

Figure

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  Fig. 1 The epithelial architecture of the stomach. It is illustrating the intricate cellular arrangement and organization within the corpus epithelium, emphasizing the presence of distinct layers and cell types. ECL: enterochromaffin-like.

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  Fig. 2 Overview of gastric organoid establishment and its applications. Adult stem cell-derived organoid established from healthy individual biopsy or patients. Pluripotent stem cell-derived organoids utilize embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC) for organoid establishment which follow the stomach development process. The successfully established organoids are maintained in the extracellular matrix with organ-specific growth factor supplements and stored at an organoid biobank. The organoid biobank has diverse applications, such as gene editing, which can be further utilized for patient organoid therapy, drug screening and development for personalized medicine, disease modelling, basic research, etc.

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  Fig. 3 Expectation of organoid-based drug development. The conventional drug development process begins with disease information followed by target selection altered in the disease condition. Once the target is selected, primary in vitro screening will be performed to search candidate compounds for pre-clinical trials. Then, in vitro hit validation with primary candidates finalize candidates for pre-clinical trials with animal models. Successful candidates after the pre-clinical trial will be transferred to a clinical trial. However, organoid-mediated drug development is initiated with a group of patients with the disease. Patient-derived organoids (PDOs) will be established and stored at an organoid biobank. Drug screening using the PDO library will discover effective drugs for the disease, and successful drug candidates will be introduced for clinical trials.

Reference

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