title: In Situ Release of VEGF Enhances Osteogenesis in 3D Porous Scaffolds Engineered with Osterix-Modified Adipose-Derived Stem Cells.
abstract: Adipose-derived stem cells (ADSCs) can differentiate into various cell types and thus have great potential for regenerative medicine. Herein, rat ADSCs were isolated; transduced with lentiviruses expressing Osterix (Osx), a transcriptional factor essential for osteogenesis. Osx overexpression upregulated key osteogenesis-related genes, such as special AT-rich binding protein 2, alkaline phosphatase, osteocalcin, and osteopontin, at both mRNA and protein levels. In addition, mineral nodule formation and alkaline phosphatase activity were enhanced in Osx-overexpressing ADSCs. The expression of dickkopf-related protein 1, a potent Wnt signaling pathway inhibitor, was also increased, whereas that of β-catenin, an intracellular signal transducer in the Wnt pathway, was decreased. β-catenin expression was partially recovered by treatment with lithium chloride, a canonical Wnt pathway activator. The Osx-expressing ADSCs were then combined with 3D gelatin-coated porous poly(ɛ-caprolactone) scaffolds with a unique release prolife of entrapped recombinant human vascular endothelial growth factor (VEGF). The controlled release of VEGF promoted osteogenic differentiation capacity in vitro. When the scaffold-ADSC complexes were transplanted into rat calvarial critical-sized defects, more bone formed on the gelatin/VEGF-coated scaffolds than on other scaffold types. Taken together, the results indicate that, Osx-overexpression promotes ADSCs' osteogenesis both in vitro and in vivo, which could be enhanced by release of VEGF.
authors.affiliation: 1 Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .|2 Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology , Shanghai, China .|3 Jiangsu Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University , Nanjing, China .
authors.forename: Wan-Lin
authors.initials: WL
authors.lastname: Xu
authors.affiliation: 1 Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .|2 Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology , Shanghai, China .
authors.forename: Hui-Shan
authors.initials: HS
authors.lastname: Ong
authors.affiliation: 1 Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .|2 Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology , Shanghai, China .
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: 1 Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .|2 Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology , Shanghai, China .
authors.forename: Sheng-Wen
authors.initials: SW
authors.lastname: Liu
authors.affiliation: 1 Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .|2 Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology , Shanghai, China .
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Liu
authors.affiliation: 1 Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .|2 Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology , Shanghai, China .
authors.forename: Kai-Hua
authors.initials: KH
authors.lastname: Zhou
authors.affiliation: 3 Jiangsu Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University , Nanjing, China .
authors.forename: Zeng-Qi
authors.initials: ZQ
authors.lastname: Xu
authors.affiliation: 4 Key Laboratory of Human Functional Genomics of Jiangsu, Department of Neurobiology, Nanjing Medical University , Nanjing, China .
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.affiliation: 5 Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology , Shanghai, China .
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 3 Jiangsu Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University , Nanjing, China .
authors.forename: Jin-Hai
authors.initials: JH
authors.lastname: Ye
authors.affiliation: 1 Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .|2 Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology , Shanghai, China .
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Yang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D003692:Delayed-Action Preparations / Q000494:pharmacology; D005260:Female; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D003692:Delayed-Action Preparations; C495181:Sp7 protein, rat; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
keywords: ADSCs; Osterix; PCL scaffolds; VEGF; control release; osteogenesis