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Current treatments for OI focus on pharmaceutical strategies to increase the amount of defective bone matrix, but do not address the underlying collagen defect. Introducing healthy donor stem cells that differentiate into osteoblasts producing normal collagen in OI patients has the potential to increase bone mass and correct the mutant collagen matrix. In this study, donor bone marrow stromal cells (BMSCs, also known as bone marrow mesenchymal stem cells) expressing both \u03b1SMACreERT2\/Ai9 progenitor reporter and osteoblast reporter Col2.3GFP were locally transplanted into the femur of OI murine (OIM) mice. One month post-transplantation, 18% of the endosteal surface was lined by donor Col2.3GFP expressing osteoblasts indicating robust engraftment. Long-term engraftment in the marrow was observed 3 and 6 months post-transplantation. The presence of Col1a2-expressing donor cell-derived cortical bone matrix was detected in transplanted OIM femurs. Local transplantation of BMSCs increased cortical thickness (+12%), the polar moment of inertia (+14%), bone strength (+30%), and stiffness (+30%) 3 months post-transplantation. Engrafted cells expressed progenitor markers CD51 and Sca-1 up to 3 months post-transplantation. Most importantly, 3 months post-transplantation donor cells maintained the ability to differentiate into Col2.3GFP+ osteoblasts in vitro, and in vivo following secondary transplantation into OIM animals. Locally transplanted BMSCs can improve cortical structure and strength, and persist as continued source of osteoblast progenitors in the OIM mouse for at least 6 months.<\/jats:p><jats:sec><jats:title\/><\/jats:sec>","DOI":"10.1002\/stem.3133","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T11:45:32Z","timestamp":1576842332000},"page":"530-541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Engraftment of skeletal progenitor cells by bone-directed transplantation improves osteogenesis imperfecta murine bone phenotype"],"prefix":"10.1093","volume":"38","author":[{"given":"Benjamin P.","family":"Sinder","sequence":"first","affiliation":[{"name":"1 Department of Reconstructive Sciences, UConn Health, Farmington, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Novak","sequence":"additional","affiliation":[{"name":"1 Department of Reconstructive Sciences, UConn Health, Farmington, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie K. Y.","family":"Wee","sequence":"additional","affiliation":[{"name":"1 Department of Reconstructive Sciences, UConn Health, Farmington, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Basile","sequence":"additional","affiliation":[{"name":"1 Department of Reconstructive Sciences, UConn Health, Farmington, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Maye","sequence":"additional","affiliation":[{"name":"1 Department of Reconstructive Sciences, UConn Health, Farmington, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brya G.","family":"Matthews","sequence":"additional","affiliation":[{"name":"1 Department of Reconstructive Sciences, UConn Health, Farmington, Connecticut"},{"name":"2 Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New 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