In Situ Release of VEGF Enhances Osteogenesis in 3D Porous Scaffolds Engineered with Osterix-Modified Adipose-Derived Stem Cells
| Autor: | Yun Zhu, Hui-Shan Ong, Jinhai Ye, Yan Zhang, Wenjun Yang, Zeng-Qi Xu, Jun Gao, Wanlin Xu, Limin Liu, Kai-Hua Zhou, Shengwen Liu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A Biomedical Engineering Bioengineering 02 engineering and technology Biochemistry Biomaterials Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Osteogenesis Animals Osteopontin biology Tissue Scaffolds Activator (genetics) Binding protein Stem Cells Wnt signaling pathway 021001 nanoscience & nanotechnology Molecular biology Rats Vascular endothelial growth factor 030104 developmental biology chemistry Adipose Tissue Delayed-Action Preparations biology.protein Osteocalcin Alkaline phosphatase Female Stem cell 0210 nano-technology Transcription Factors |
| Zdroj: | Tissue engineering. Part A. 23(9-10) |
| ISSN: | 1937-335X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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