[Mesenchymal stem cells modified with Runt-related transcription factor 2 promote bone regeneration in rabbit mandibular distraction osteogenesis].

OBJECTIVE This work investigated mesenchymal stem cells (MSCs) modified with Runt-related transcription factor 2 (Runx2) therapy for bone regeneration in rabbit mandibular distraction osteogenesis. METHODS Forty-eight New Zealand mature white rabbits were randomly divided into three groups after the rabbit model of mandibular distraction osteogenesis was established: reconstruction plasmid modified with Runx2 (group A), plasmid without Runx2 (group B), and the same dose of saline as control (group C). At the fifth day of distraction phase, MSCs with reconstruction plasmid modified with adv-hRunx2-gfp were injected into the distraction gap of group A. MSCs with reconstruction plasmid modified with adv-gfp was injected into the distraction gap of group B, whereas group C was injected with the same dose of saline. At 8 weeks after injection, all animals were sacrificed, and the distracted mandibles were harvested. The general imaging histological observation and three-point bending test were used for evaluation. RESULTS CT plain scan and histological analysis confirmed that the amount of new bone forming in the distraction gap of group A was significantly higher than those in groups B and C. Dual-energy X ray and three-point bending test results also showed that the bone mineral density, bone mineral content, and maximum load of the distraction gap of group A were significantly higher than those of groups B and C (P<0.01). CONCLUSION Runx2-ex vivo gene therapy based on MSCs can effectively promote the bone regeneration in rabbit mandibular distraction osteogenesis and shorten the stationary phase. Therefore, reconstruction of craniofacial fracture would be a valuable strategy

[1]  Zongyang Sun,et al.  Mandibular distraction osteogenesis assisted by cell-based tissue engineering: a systematic review. , 2015, Orthodontics & craniofacial research.

[2]  Chen Li,et al.  Potential of Mesenchymal Stem Cells by Adenovirus-Mediated Erythropoietin Gene Therapy Approaches for Bone Defect , 2014, Cell Biochemistry and Biophysics.

[3]  Wei Tang,et al.  New bone formation enhanced by ADSCs overexpressing hRunx2 during mandibular distraction osteogenesis in osteoporotic rabbits , 2014, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[4]  T. He,et al.  Adenovirus-Mediated Gene Transfer in Mesenchymal Stem Cells Can Be Significantly Enhanced by the Cationic Polymer Polybrene , 2014, PloS one.

[5]  Fengcai Wei,et al.  Effects of allogenous periosteal-derived cells transfected with adenovirus-mediated BMP-2 on repairing defects of the mandible in rabbits. , 2013, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[6]  Xuanping Huang,et al.  [Experimental study on transplantation of bone morphogenetic protein-2 gene transfected bone mesenchymal stem cells compounded with Pluronic F-127 for promoting bone regeneration in rabbit mandibular distraction]. , 2013, Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology.

[7]  Hongli Sun,et al.  Stem cell therapy remediates reconstruction of the craniofacial skeleton after radiation therapy. , 2013, Stem cells and development.

[8]  T. Alliston,et al.  Chondrocyte-intrinsic Smad3 represses Runx2-inducible matrix metalloproteinase 13 expression to maintain articular cartilage and prevent osteoarthritis. , 2012, Arthritis and rheumatism.

[9]  Xiangrong Cheng,et al.  Delivery of PDGF-B and BMP-7 by mesoporous bioglass/silk fibrin scaffolds for the repair of osteoporotic defects. , 2012, Biomaterials.

[10]  W. Tawackoli,et al.  Gene-modified adult stem cells regenerate vertebral bone defect in a rat model. , 2011, Molecular pharmaceutics.

[11]  I.S. Kim,et al.  Osteogenic Responses of Human Mesenchymal Stromal Cells to Static Stretch , 2010, Journal of dental research.

[12]  Z. Zhao,et al.  Healing Cranial Defects with AdRunx2-transduced Marrow Stromal Cells , 2007, Journal of dental research.

[13]  Naoki Ishiguro,et al.  Transplantation of culture expanded bone marrow cells and platelet rich plasma in distraction osteogenesis of the long bones. , 2007, Bone.

[14]  N. Ishiguro,et al.  Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis--a preliminary result of three cases. , 2004, Bone.

[15]  M. Burnett,et al.  Local Delivery of Marrow-Derived Stromal Cells Augments Collateral Perfusion Through Paracrine Mechanisms , 2004, Circulation.

[16]  S. K. Zaidi,et al.  Temporal and Spatial Parameters of Skeletal Gene Expression: Targeting RUNX Factors and their Coregulatory Proteins to Subnuclear Domains , 2003, Connective tissue research.

[17]  N. Kanatani,et al.  Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures , 2001, The Journal of cell biology.

[18]  Zhao Hong-bi.  Runx2 and Signal Transduction of Osteoblast Differentiation , 2007 .

[19]  Luigi Naldini,et al.  Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics , 2001, Nature Medicine.