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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.<\/jats:p>","DOI":"10.3390\/cells13090729","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T08:08:27Z","timestamp":1713859707000},"page":"729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7613-5249","authenticated-orcid":false,"given":"Ha-Young","family":"Kim","sequence":"first","affiliation":[{"name":"Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mentine","family":"Charton","sequence":"additional","affiliation":[{"name":"Precision Medicine Center, Future Innovation Research Division, Seoul National University Bundang Hospital, Seongnam 13605, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Hee","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Research Administration Team, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Young","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9524-9981","authenticated-orcid":false,"given":"Jinho","family":"Kim","sequence":"additional","affiliation":[{"name":"Precision Medicine Center, Future Innovation Research Division, Seoul National University Bundang Hospital, Seongnam 13605, Republic of Korea"},{"name":"Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sejoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Precision Medicine Center, Future Innovation Research Division, Seoul National University Bundang Hospital, Seongnam 13605, Republic of Korea"},{"name":"Department of Pathology, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Hun","family":"Ohn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baek Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-7365","authenticated-orcid":false,"given":"Chan Yeong","family":"Heo","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"ref_1","unstructured":"Rosen, C.J. 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