Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Aug;21(6):1631-1647.
doi: 10.1007/s12015-025-10894-9. Epub 2025 May 19.

Latest Advanced Techniques for Improving Intestinal Organoids Limitations

Affiliations
Review

Latest Advanced Techniques for Improving Intestinal Organoids Limitations

Lisa Tonini et al. Stem Cell Rev Rep. 2025 Aug.

Abstract

Intestinal organoids are valuable tools across different disciplines, from a clinical aspect to the biomedical research, providing a unique perspective on the complexity of the gastrointestinal system. They are alternatives to common cell lines as they can offer insights into architectural functionality and reduce the use of animal models. A deeper understanding of their organoid characteristics is required to harness their full potential. Despite their beneficial uses and multiple advantages, organoids have limitations that remain unaddressed. This review aims to elucidate the principal limitations of intestinal organoids, investigate structural defects such as the deficiency in a vascularized and lymphatic system, and absence of the microbiome, restrictions in mimicking the physiological gut model, including the lack of an acid-neutralizing system or a shortage of digestive enzymes, and the difficulties in their long-term maintenance and polarity accessibility. Development of innovative techniques to address these limitations will lead to improve in vivo recapitulation and pioneering further advancements in this field.

Keywords: Advanced Strategies; Intestinal Organoids; Limitations and Challenges; Optimization.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical Approval: Not applicable. Consent To Participate: Not applicable. Consent To Publish: Corresponding authors on behalf of all authors, give our consent for the publication of details acquired during preparation the text to be published in the Stem Cell Reviews and Reports Journal. Competing interests: The authors declare no conflict of interest.

Similar articles

Cited by

References

    1. Volk, N., & Lacy, B. (2017). Anatomy and physiology of the small bowel. Gastrointestinal Endoscopy Clinics of North America, 27(1), 1–13. - PubMed
    1. Ali, M., et al. (2015). Updated global burden of cholera in endemic countries. Plos Neglected Tropical Diseases, 9(6), e0003832. - PubMed - PMC
    1. Oh, S., & Yoo, Y. B. (2019). Epithelial-Mesenchymal interactions for the development of intestinal villi. Dev Reprod, 23(4), 305–311. - PubMed - PMC
    1. Di Sabatino, A., et al. (2023). Role of mucosal immunity and epithelial-vascular barrier in modulating gut homeostasis. Internal and Emergency Medicine, 18(6), 1635–1646. - PubMed - PMC
    1. Siqueira, M. D. S., Ribeiro, R. M., & Travassos, L. H. (2018). Autophagy and its interaction with intracellular bacterial pathogens. Frontiers in Immunology, 9, 935. - PubMed - PMC

LinkOut - more resources