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Thus, identifying adjunctive treatments to optimize bone regeneration during CD is an unmet clinical need. Platelet-derived growth factor (PDGF)-BB plays a central role in cell growth and differentiation. The aim of this study was to characterize mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) in vitro and evaluate their therapeutic effect when injected into the bone tunnel at the time of CD in an in vivo rabbit model of steroid-associated ONFH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In vitro studies<jats:italic>:<\/jats:italic>Rabbit MSCs were transduced with a lentivirus vector carrying the human PDGF-BB gene under the control of either the cytomegalovirus (CMV) or phosphoglycerate (PGK) promoter. The proliferative rate, PDGF-BB expression level, and osteogenic differentiation capacity of unmodified MSCs, CMV-PDGF-BB-MSCs, and PGK-PDGF-BB-MSCs were assessed. In vivo studies: Twenty-four male New Zealand white rabbits received an intramuscular (IM) injection of methylprednisolone 20\u00a0mg\/kg. Four weeks later, the rabbits were divided into four groups: the CD group, the hydrogel [HG, (a collagen-alginate mixture)] group, the MSC group, and the PGK-PDGF-BB-MSC group. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vitro studies<jats:italic>:<\/jats:italic>PGK-PDGF-BB-MSCs proliferated more rapidly than unmodified MSCs (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and CMV-PDGF-BB-MSCs (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) at days 3 and 7. CMV-PDGF-BB-MSCs demonstrated greater PDGF-BB expression than PGK-PDGF-BB-MSCs (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). However, PGK-PDGF-BB-MSCs exhibited greater alkaline phosphatase staining at 14\u00a0days (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), and osteogenic differentiation at 28\u00a0days (<jats:italic>P<\/jats:italic>\u2009=\u20090.07) than CMV-PDGF-BB-MSCs. In vivo<jats:italic>:<\/jats:italic>The PGK-PDGF-BB-MSC group had a trend towards greater bone mineral density (BMD) than the CD group (<jats:italic>P<\/jats:italic>\u2009=\u20090.074). The PGK-PDGF-BB-MSC group demonstrated significantly lower numbers of empty lacunae (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), greater osteoclast density (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), and greater angiogenesis (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) than the other treatment groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may reduce progression of osteonecrosis and enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13287-021-02572-7","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T18:08:42Z","timestamp":1631729322000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1623-6336","authenticated-orcid":false,"given":"Roberto Alfonso","family":"Guzman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyedsina","family":"Moeinzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Lui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter W.","family":"Storaci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaysie","family":"Tam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elijah Ejun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Utsunomiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Rhee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzhi Peter","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart B.","family":"Goodman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"issue":"12","key":"2572_CR1","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.2106\/JBJS.19.01271","volume":"102","author":"MA Mont","year":"2020","unstructured":"Mont MA, et al. 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