title: Mesenchymal stem cell expression of SDF-1β synergizes with BMP-2 to augment cell-mediated healing of critical-sized mouse calvarial defects.
abstract: Bone has the potential for spontaneous healing. This process, however, often fails in patients with comorbidities. Tissue engineering combining functional cells, biomaterials and osteoinductive cues may provide alternative treatment strategies. We have recently demonstrated that stromal cell-derived factor-1β (SDF-1β) works in concert with bone morphogenetic protein-2 (BMP-2) to potentiate osteogenic differentiation of bone marrow-derived mesenchymal stem/stromal cells (BMSCs). Here, we test the hypothesis that SDF-1β overexpressed in Tet-Off-SDF-1β BMSCs, delivered on acellular dermal matrix (ADM), synergistically augments BMP-2-induced healing of critical-sized mouse calvarial defects. BMSC therapies alone showed limited bone healing, which was increased with co-delivery of BMP-2. This was further enhanced in Tet-Off-SDF-1β BMSCs + BMP-2. Only limited BMSC retention on ADM constructs was observed after 4 weeks in vivo, which was increased with BMP-2 co-delivery. In vitro cell proliferation studies showed that supplementing BMP-2 to Tet-Off BMSCs significantly increased the cell number during the first 24 h. Consequently, the increased cell numbers decreased the detectable BMP-2 levels in the medium, but increased cell-associated BMP-2. The data suggest that SDF-1β provides synergistic effects supporting BMP-2-induced, BMSC-mediated bone formation and appears suitable for optimization of bone augmentation in combination therapy protocols. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Herberg
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA, USA.|Department of Cellular and Molecular Biology, Universidad Central del Caribe, Bayamón, Puerto Rico, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Aguilar-Perez
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA, USA.|Department of Oral Biology, Georgia Regents University, Augusta, GA, USA.
authors.forename: R Nicole
authors.initials: RN
authors.lastname: Howie
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA, USA.
authors.forename: Galina
authors.initials: G
authors.lastname: Kondrikova
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA, USA.
authors.forename: Sudharsan
authors.initials: S
authors.lastname: Periyasamy-Thandavan
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA, USA.|Department of Oral Biology, Georgia Regents University, Augusta, GA, USA.|Department of Orthopedic Surgery, Georgia Regents University, Augusta, GA, USA.|Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, USA.
authors.forename: Mohammed E
authors.initials: ME
authors.lastname: Elsalanty
authors.affiliation: Department of Orthopedic Surgery, Georgia Regents University, Augusta, GA, USA.|Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, GA, USA.|Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, USA.
authors.forename: Xingming
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA, USA.|Department of Orthopedic Surgery, Georgia Regents University, Augusta, GA, USA.|Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, GA, USA.|Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, USA.|Charlie Norwood VA Medical Centre, Augusta, GA, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Hill
authors.affiliation: Department of Oral Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Cray
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D054377:Chemokine CXCL12 / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000737:chemistry*; D017102:Fracture Healing; D005786:Gene Expression Regulation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010012:Osteogenesis; D012886:Skull / Q000293:injuries / Q000378:metabolism / Q000473:pathology
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse
keywords: BMP-2; BMSCs; SDF-1/CXCL12; bone formation; stem cell transplantation