Institute of Clinical Molecular Biology, University of Kiel, Kiel, Germany.
Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein, Kiel, Germany.
Front Immunol. 2020 Dec 21;11:573562. doi: 10.3389/fimmu.2020.573562. eCollection 2020.
Individualised cellular models of disease are a key tool for precision medicine to recapitulate chronic inflammatory processes. Organoid models can be derived from induced pluripotent stem cells (iPSCs) or from primary stem cells . These models have been emerging over the past decade and have been used to reconstruct the respective organ-specific physiology and pathology, at an unsurpassed depth. In cancer research, patient-derived cancer organoids opened new perspectives in predicting therapy response and provided novel insights into tumour biology. In precision medicine of chronic inflammatory disorders, stem-cell based organoid models are currently being evaluated in pre-clinical pharmacodynamic studies (clinical studies in a dish) and are employed in clinical studies, e.g., by re-transplanting autologous epithelial organoids to re-establish intestinal barrier integrity. A particularly exciting feature of iPSC systems is their ability to provide insights into organ systems and inflammatory disease processes, which cannot be monitored with clinical biopsies, such as immune reactions in neurodegenerative disorders. Refinement of differentiation protocols, and next-generation co-culturing methods, aimed at generating self-organised, complex tissues , will be the next logical steps. In this mini-review, we critically discuss the current state-of-the-art stem cell and organoid technologies, as well as their future impact, potential and promises in combating immune-mediated chronic diseases.
个体化细胞疾病模型是精准医学重现慢性炎症过程的关键工具。类器官模型可源自诱导多能干细胞 (iPSC) 或源自原代干细胞。这些模型在过去十年中不断涌现，并被用于以无与伦比的深度重建各自的器官特异性生理学和病理学。在癌症研究中，患者来源的癌症类器官为预测治疗反应开辟了新的视角，并为肿瘤生物学提供了新的见解。在慢性炎症性疾病的精准医学中，基于干细胞的类器官模型目前正在临床前药效学研究（在培养皿中的临床研究）中进行评估，并在临床研究中得到应用，例如，通过重新移植自体上皮类器官来重建肠道屏障完整性。iPSC 系统的一个特别令人兴奋的特点是它们能够深入了解器官系统和炎症性疾病过程，而这些过程无法通过临床活检来监测，例如神经退行性疾病中的免疫反应。改进分化方案和下一代共培养方法，旨在生成自组织的复杂组织，将是下一个合乎逻辑的步骤。在这篇迷你综述中，我们批判性地讨论了当前最先进的干细胞和类器官技术，以及它们在对抗免疫介导的慢性疾病方面的未来影响、潜力和承诺。
