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Stem Cells and Organoid Technology in Precision Medicine in Inflammation: Are We There Yet?

机译:干细胞和有机体技术在炎症的精密药物中:我们还在吗?

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摘要

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 ex vivo. 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 in vitro, 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.
机译:个性化的细胞疾病模型是精密药物重新承载慢性炎症过程的关键工具。有机体模型可以衍生自诱导的多能干细胞(IPSC)或来自初级干细胞离体。这些模型在过去十年中已经出现了,已被用于在无与伦比的深度下重建各自的器官特异性生理学和病理学。在癌症研究中,患者衍生的癌症有机体在预测治疗响应中开启了新的视角,并为肿瘤生物学提供了新的洞察。在慢性炎症疾病的精​​确药物中,目前在临床前药效学研究中评估干细胞的有机体模型(盘中的临床研究),并且在临床研究中使用,例如通过再移植自体上皮有机体来重新建立肠道屏障完整性。 iPSC集系统的一个特别令人兴奋的特征是它们提供见解器官系统和炎性疾病的进程,这是不能用临床活检,如神经变性疾病的免疫反应进行监测的能力。分化方案的细化和下一代共培养方法,旨在在体外产生自组织,复杂组织,将是下一个逻辑步骤。在这个迷你审查中,我们严格讨论在打击免疫介导的慢性疾病的当前状态的最先进的干细胞和组织体技术,以及他们未来的影响,潜力和承诺。

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