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Herein we show that hematopoietic stem cell (HSC) therapy holds promise in treating OI. Using single-cell HSC transplantation in lethally irradiated oim\/oim mice, we demonstrate significant improvements in bone morphometric, mechanics, and turnover parameters. Importantly, we highlight that HSCs cause these improvements due to their unique property of differentiating into osteoblasts\/osteocytes, depositing normal collagen\u2014an attribute thus far assigned only to mesenchymal stem\/stromal cells. To confirm HSC plasticity, lineage tracing was done by transplanting oim\/oim with HSCs from two specific transgenic mice\u2014VavR, in which all hematopoietic cells are GFP+ and pOBCol2.3GFP, where GFP is expressed only in osteoblasts\/osteocytes. In both models, transplanted oim\/oim mice demonstrated GFP+ HSC-derived osteoblasts\/osteocytes in bones. These studies unequivocally establish that HSCs differentiate into osteoblasts\/osteocytes, and HSC transplantation can provide a new translational approach for OI.<\/jats:p>","DOI":"10.1002\/stem.3432","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T09:59:27Z","timestamp":1636624767000},"page":"1457-1477","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hematopoietic Stem Cell-Derived Functional Osteoblasts Exhibit Therapeutic Efficacy in a Murine Model of Osteogenesis Imperfecta"],"prefix":"10.1093","volume":"39","author":[{"given":"In-Hong","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine \u00a0Medical University of South Carolina, Charleston, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uday K.","family":"Baliga","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine \u00a0Medical University of South Carolina, Charleston, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongren","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics \u00a0Medical University of South Carolina, Charleston, South Carolina, USA"},{"name":"Clemson-MUSC Joint Bioengineering Program Medical University of South Carolina, Charleston, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shikhar","family":"Mehrotra","sequence":"additional","affiliation":[{"name":"Department of Surgery \u00a0Medical University of South Carolina, Charleston, South Carolina, USA"},{"name":"Hollings Cancer Center \u00a0Medical University of South Carolina, Charleston, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics \u00a0Medical University of South Carolina, Charleston, South Carolina, USA"},{"name":"Department of Oral Health Sciences \u00a0Medical University of South Carolina, Charleston, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda C.","family":"LaRue","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine \u00a0Medical University of South Carolina, Charleston, South Carolina, USA"},{"name":"Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7019-5363","authenticated-orcid":false,"given":"Meenal","family":"Mehrotra","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine \u00a0Medical University of South Carolina, Charleston, South Carolina, USA"},{"name":"Center for Oral Health Research \u00a0Medical University of South Carolina, Charleston, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"issue":"10028","key":"2022022511281469800_stem3432-bib-0001","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/S0140-6736(15)00728-X","article-title":"Osteogenesis 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