PDF(Pubmed)
Abstract：
Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Initially, transcriptomic profiling of individual cells isolated from patient lesional tissues unveiled intralesional molecular and cellular heterogeneity. Leveraging these insights, we established patient-derived organoids (PDOs) using primary cells obtained from patient FD lesions. Evaluation of PDOs demonstrated preservation of fibrosis-associated constituent cell types and transcriptional signatures observed in FD lesions. Additionally, PDOs retained distinct constellations of genomic and metabolic alterations characteristic of FD. Histological evaluation further corroborated the fidelity of PDOs in recapitulating important phenotypic features of FD that underscore their pathophysiological relevance. Our findings represent meaningful progress in the field, as they open up the possibility for in vitro modeling of rare bone lesions in a three-dimensional context and may signify the first step towards creating a personalized platform for research and therapeutic studies.
摘要：
纤维发育不良（FD）是一种罕见的骨骼疾病，其特征是用良性纤维骨组织代替正常骨骼。缺乏合适的研究模型阻碍了我们对病理生理学和治疗选择的理解的发展。在这项研究中,我们开发了一种体外器官型模型，能够概括FD的关键内在和表型特性。最初，从患者病变组织中分离的单个细胞的转录组学分析揭示了病变内分子和细胞异质性。利用这些见解，我们使用从患者FD病变获得的原代细胞建立了患者来源的类器官(PDO).PDO的评估证明了在FD病变中观察到的纤维化相关组成细胞类型和转录特征的保留。此外,PDO保留了FD特有的基因组和代谢改变的不同星座。组织学评估进一步证实了PDO的保真度，以概括FD的重要表型特征，强调了其病理生理相关性。我们的发现代表了该领域的有意义的进展，因为它们为三维背景下罕见骨病变的体外建模开辟了可能性，并且可能标志着为研究和治疗研究创建个性化平台的第一步。
