title: Controlled chondrogenesis from adipose-derived stem cells by recombinant transforming growth factor-β3 fusion protein in peptide scaffolds.
abstract: Adipose-derived stem cells (ADSCs) are promising for cartilage repair due to their easy accessibility and chondrogenic potential. Although chondrogenesis of transforming growth factor-β (TGF-β) mediated mesenchymal stem cells (MSCs) is well established in vitro, clinical tissue engineering requires effective and controlled delivery of TGF-β in vivo. In this work, a self-assembled peptide scaffold was employed to construct cartilages in vivo through the chondrogenesis from ADSCs controlled by recombinant fusion protein LAP-MMP-mTGF-β3 that was transfected by lentiviral vectors. During this course, the addition of matrix metalloproteinases (MMPs) can trigger the release of mTGF-β3 from the recombinant fusion protein of LAP-MMP-mTGF-β3 in the combined scaffolds, thus stimulating the differentiation of ADSCs into chondrogenesis. The specific expression of cartilage genes was analyzed by real-time polymerase chain reaction and Western blot. The expression of chondrocytic markers was obviously upregulated to a higher level compared to the one by commonly used TGF-β3 alone. After 3 weeks of in vitro culturing, the hybrids with differentiated chondrogenesis were then injected subcutaneously into nude mice and retrieved after 4 weeks of culturing in vivo. Histological analysis also confirmed that the recombinant fusion protein was more effective for the formation of cartilage matrix than the cases either with TGF-β3 alone or without LAP-MMP-mTGF-β3 (P<0.05). This study demonstrates that controlled local delivery of the LAP-MMP-mTGF-β3 constructs can accelerate differentiation of ADSCs into the cartilage in vivo, which indicates the great potential of this hybrid in rapid therapy of osteoarthritis.
authors.affiliation: Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China. Electronic address: Yang.Dan.daniel@gmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Dan
authors.affiliation: Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Shu-hua
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Guo-hui
authors.initials: GH
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Zeng-wu
authors.initials: ZW
authors.lastname: Shao
authors.affiliation: Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Cao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Bao-jun
authors.initials: BJ
authors.lastname: Xiao
authors.affiliation: Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Province Key Laboratory of Industrial Biotechnology, Faculty of Materials Science and Engineering, Hubei University, Wuhan, People's Republic of China.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Province Key Laboratory of Industrial Biotechnology, Faculty of Materials Science and Engineering, Hubei University, Wuhan, People's Republic of China. Electronic address: shuilin.wu@gmail.com.
authors.forename: Shuilin
authors.initials: S
authors.lastname: Wu
authors.affiliation: Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Province Key Laboratory of Industrial Biotechnology, Faculty of Materials Science and Engineering, Hubei University, Wuhan, People's Republic of China.
authors.forename: Tainjin
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China. Electronic address: paul.chu@cityu.edu.hk.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Chu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis / Q000187:drug effects*; D018093:Gelatinases / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D010003:Osteoarthritis / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000943:Antigens, Differentiation; D022782:CCAAT-Enhancer-Binding Protein-beta; D011993:Recombinant Fusion Proteins; C509045:Tgfb3 protein, mouse; D053782:Transforming Growth Factor beta3; D018093:Gelatinases
keywords: Adipose-derived stem cells; Cartilage; Hydrogel; Osteoarthritis; Scaffolds