{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:13:27Z","timestamp":1785510807322,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"kind donation of Hans Horsting and Mary Horsting-Stuit of the Horstingstuit Foundation","award":["PUTJD1009"],"award-info":[{"award-number":["PUTJD1009"]}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PUTJD1009"],"award-info":[{"award-number":["PUTJD1009"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Mesenchymal stem cells (MSCs) are a valuable cell model to study the bone pathology of Osteogenesis Imperfecta (OI), a rare genetic collagen-related disorder characterized by bone fragility and skeletal dysplasia. We aimed to generate a novel OI induced mesenchymal stem cell (iMSC) model from induced pluripotent stem cells (iPSCs) derived from human dermal fibroblasts. For the first time, OI iMSCs generation was based on an intermediate neural crest cell (iNCC) stage. (2) Skin fibroblasts from healthy individuals and OI patients were reprogrammed into iPSCs and subsequently differentiated into iMSCs via iNCCs. (3) Successful generation of iPSCs from acquired fibroblasts was confirmed with changes in cell morphology, expression of iPSC markers SOX2, NANOG, and OCT4 and three germ-layer tests. Following differentiation into iNCCs, cells presented increased iNCC markers including P75NTR, TFAP2A, and HNK-1 and decreased iPSC markers, shown to reach the iNCC stage. Induction into iMSCs was confirmed by the presence of CD73, CD105, and CD90 markers, low expression of the hematopoietic, and reduced expression of the iNCC markers. iMSCs were trilineage differentiation-competent, confirmed using molecular analyses and staining for cell-type-specific osteoblast, adipocyte, and chondrocyte markers. (4) In the current study, we have developed a multipotent in vitro iMSC model of OI patients and healthy controls able to differentiate into osteoblast-like cells.<\/jats:p>","DOI":"10.3390\/ijms25063417","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T06:58:39Z","timestamp":1710745119000},"page":"3417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["In Vitro Modelling of Osteogenesis Imperfecta with Patient-Derived Induced Mesenchymal Stem Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Lauria","family":"Claeys","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Rare Bone Disease Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Movement Sciences, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4682-0402","authenticated-orcid":false,"given":"Lidiia","family":"Zhytnik","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Rare Bone Disease Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Movement Sciences, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Traumatology and Orthopaedics, The University of Tartu, 50410 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ventura","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Rare Bone Disease Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Movement Sciences, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisanne E.","family":"Wisse","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5399-676X","authenticated-orcid":false,"given":"Elisabeth M. W.","family":"Eekhoff","sequence":"additional","affiliation":[{"name":"Rare Bone Disease Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Movement Sciences, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC Location Vrije Universiteit, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-7115","authenticated-orcid":false,"given":"Gerard","family":"Pals","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Bravenboer","sequence":"additional","affiliation":[{"name":"Amsterdam Movement Sciences, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Clinical Chemistry, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4416-3875","authenticated-orcid":false,"given":"Vivi M.","family":"Heine","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam Neuroscience, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Micha","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Rare Bone Disease Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Movement Sciences, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1136\/jmg.28.7.433","article-title":"Osteogenesis imperfecta: Translation of mutation to phenotype","volume":"28","author":"Byers","year":"1991","journal-title":"J. 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