Marr Elizabeth E, Gnecco Juan S, Missmer Stacey A, Hawkins Shannon M, Osteen Kevin G, Hummelshoj Lone, Greaves Erin, Bruner-Tran Kaylon L
Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA.
Mol Hum Reprod. 2025 Jul 3;31(3). doi: 10.1093/molehr/gaaf024.
The aetiology of endometriosis remains poorly understood. In vitro model systems provide the opportunity to identify the mechanisms driving disease pathogenesis using human cells. Three-dimensional models, particularly organoid systems, have revolutionized how we study epithelial biology and are powerful tools for modelling endometriosis. As an emerging model system, it is important to define protocols and identify the remaining challenges surrounding endometrial organoid culture to increase reproducibility and scientific rigour in endometriosis research. The World Endometriosis Research Foundation (WERF) established an international working group comprised of experts using in vitro approaches for the study of endometriosis. This working group harmonized protocols and documentation of existing and emerging organoid systems to maximize comparison and replication across the field and guide specific research hypotheses testing. This evaluation of organoid protocols, limitations, challenges, and alternative approaches assessed both published and grey literature papers across several disciplines pertinent to endometriosis research. Recommendations for protocol and documentation harmonization are presented, and we created the first-ever decision tree diagram to guide and facilitate the selection of existing models best suited for specific areas of endometriosis research. Rigorous and systematic assessment of emerging organoid systems, recognizing the inferential strengths and limitations of these approaches, is vital for endometriosis research. This comprehensive review of the benefits, limitations, and utilization of organoid models, as well as the consequent integration of protocols and documentation, will contribute to the scientific knowledge base by maximizing the reproducibility, comparability, and interpretation of research studies in endometriosis. Additionally, these newly developed protocols and documentation should serve as a resource for, and facilitate collaboration between, endometriosis investigators using organoids in their research methods.
子宫内膜异位症的病因仍未得到充分了解。体外模型系统为利用人类细胞识别驱动疾病发病机制提供了机会。三维模型，尤其是类器官系统，彻底改变了我们研究上皮生物学的方式，是模拟子宫内膜异位症的强大工具。作为一种新兴的模型系统，定义方案并识别围绕子宫内膜类器官培养的剩余挑战，对于提高子宫内膜异位症研究的可重复性和科学严谨性至关重要。世界子宫内膜异位症研究基金会（WERF）成立了一个国际工作组，其成员由使用体外方法研究子宫内膜异位症的专家组成。该工作组协调了现有和新兴类器官系统的方案和文档，以最大限度地在整个领域进行比较和复制，并指导特定研究假设的检验。这项对类器官方案、局限性、挑战和替代方法的评估，评估了与子宫内膜异位症研究相关的多个学科的已发表和灰色文献论文。本文提出了方案和文档协调的建议，并创建了有史以来第一个决策树图，以指导和促进选择最适合子宫内膜异位症研究特定领域的现有模型。对新兴类器官系统进行严格和系统的评估，认识到这些方法的推理优势和局限性，对子宫内膜异位症研究至关重要。对类器官模型的益处、局限性和应用，以及随之而来的方案和文档整合进行的全面综述，将通过最大限度地提高子宫内膜异位症研究的可重复性、可比性和解释性，为科学知识库做出贡献。此外，这些新制定的方案和文档应作为使用类器官进行研究的子宫内膜异位症研究人员的资源，并促进他们之间的合作。
