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Advances in the 3D Culture Systems and Organoids for Disease Modeling and Therapeutics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 1465

Special Issue Editor

Special Issue Information

Dear Colleagues,

This Special Issue highlights the recent advances in 3D culture systems and organoids for disease modeling and therapeutic development. These innovative systems provide more physiologically relevant models than traditional 2D cultures, aiding in the breakthroughs in understanding disease processes and creating new therapeutic strategies. We welcome submissions across a broad range of topics, including the use of 3D models and organoids in drug discovery, regenerative medicine, and biomaterials for therapeutic applications. Studies exploring the molecular mechanisms involved in disease progression and treatment responses are also encouraged. Additionally, novel approaches utilizing 3D systems in cancer, immunology, and other fields are welcome. The aim of this Special Issue is to provide a platform for interdisciplinary research that advances personalized medicine and therapeutic innovation.

Prof. Dr. Su-Yun Lyu
Guest Editor

Manuscript Submission Information

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Keywords

  • 3D culture systems
  • organoids
  • disease modeling
  • drug discovery
  • regenerative
  • medicine biomaterials
  • molecular mechanisms
  • cancer
  • immunology
  • personalized medicine

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Published Papers (1 paper)

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Review

33 pages, 1777 KB  
Review
Immunomodulatory Natural Products in Cancer Organoid-Immune Co-Cultures: Bridging the Research Gap for Precision Immunotherapy
by Chang-Eui Hong and Su-Yun Lyu
Int. J. Mol. Sci. 2025, 26(15), 7247; https://doi.org/10.3390/ijms26157247 - 26 Jul 2025
Viewed by 1087
Abstract
Natural products demonstrate potent immunomodulatory properties through checkpoint modulation, macrophage polarization, and T cell/natural killer (NK) cell activation. While cancer organoid-immune co-culture platforms enable physiologically relevant modeling of tumor–immune interactions, systematic investigation of natural product immunomodulation in these systems remains entirely unexplored. We [...] Read more.
Natural products demonstrate potent immunomodulatory properties through checkpoint modulation, macrophage polarization, and T cell/natural killer (NK) cell activation. While cancer organoid-immune co-culture platforms enable physiologically relevant modeling of tumor–immune interactions, systematic investigation of natural product immunomodulation in these systems remains entirely unexplored. We conducted a comprehensive literature analysis examining natural products tested in cancer organoids, immunomodulatory mechanisms from traditional models, technical advances in organoid-immune co-cultures, and standardization requirements for clinical translation. Our analysis reveals a critical research gap: no published studies have investigated natural product-mediated immunomodulation using organoid-immune co-culture systems. Even though compounds like curcumin, resveratrol, and medicinal mushroom polysaccharides show extensive immunomodulatory effects in two-dimensional (2D) cultures, and organoid technology achieves high clinical correlation for drug response prediction, all existing organoid studies focus exclusively on direct cytotoxicity. Technical challenges include compound stability, limited matrix penetration requiring substantially higher concentrations than 2D cultures, and maintaining functional immune populations in three-dimensional (3D) systems. The convergence of validated organoid-immune co-culture platforms, Food and Drug Administration (FDA) regulatory support through the Modernization Act 2.0, and extensive natural product knowledge creates unprecedented opportunities. Priority research directions include systematic screening of immunomodulatory natural products in organoid-immune co-cultures, development of 3D-optimized delivery systems, and clinical validation trials. Success requires moving beyond cytotoxicity-focused studies to investigate immunomodulatory mechanisms in physiologically relevant 3D systems, potentially unlocking new precision cancer immunotherapy approaches. Full article
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