Department of Biomedical Sciences, University of Groningen (RUG) and University Medical Center Groningen (UMCG), Groningen, The Netherlands.
Department of Radiation Oncology, University of Groningen (RUG) and University Medical Center Groningen (UMCG), Groningen, The Netherlands.
Stem Cells. 2024 Jun 14;42(6):499-508. doi: 10.1093/stmcls/sxae023.
Inter-individual variation largely influences disease susceptibility, as well as response to therapy. In a clinical context, the optimal treatment of a disease should consider inter-individual variation and formulate tailored decisions at an individual level. In recent years, emerging organoid technologies promise to capture part of an individual's phenotypic variability and prove helpful in providing clinically relevant molecular insights. Organoids are stem cell-derived 3-dimensional models that contain multiple cell types that can self-organize and give rise to complex structures mimicking the organization and functionality of the tissue of origin. Organoids therefore represent a more faithful recapitulation of the dynamics of the tissues of interest, compared to conventional monolayer cultures, thus supporting their use in evaluating disease prognosis, or as a tool to predict treatment outcomes. Additionally, the individualized nature of patient-derived organoids enables the use of autologous organoids as a source of transplantable material not limited by histocompatibility. An increasing amount of preclinical evidence has paved the way for clinical trials exploring the applications of organoid-based technologies, some of which are in phase I/II. This review focuses on the recent progress concerning the use of patient-derived organoids in personalized medicine, including (1) diagnostics and disease prognosis, (2) treatment outcome prediction to guide therapeutic advice, and (3) organoid transplantation or cell-based therapies. We discuss examples of these potential applications and the challenges associated with their future implementation.
个体间的差异在很大程度上影响疾病的易感性以及对治疗的反应。在临床环境中，疾病的最佳治疗应考虑个体间的差异，并在个体层面制定针对性的决策。近年来，新兴的类器官技术有望捕捉到个体表型变异的一部分，并有助于提供与临床相关的分子见解。类器官是由干细胞衍生而来的三维模型，包含多种能够自我组织并产生模拟起源组织的组织结构和功能的细胞类型。因此，与传统的单层培养相比，类器官更能真实地再现感兴趣组织的动态，从而支持将其用于评估疾病预后或作为预测治疗结果的工具。此外，患者来源的类器官的个体化性质使得可以使用自体类器官作为可移植材料的来源，而不受组织相容性的限制。越来越多的临床前证据为探索类器官技术应用的临床试验铺平了道路，其中一些处于 I/II 期。本综述重点介绍了患者来源的类器官在个性化医疗中的最新进展，包括（1）诊断和疾病预后，（2）治疗结果预测以指导治疗建议，以及（3）类器官移植或基于细胞的治疗。我们讨论了这些潜在应用的例子以及它们未来实施所面临的挑战。
