In vitro engineered cartilage using synovium-derived mesenchymal stem cells with injectable gellan hydrogels |
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| Authors: | Jiabing Fan Yihong Gong Li Ren Rohan R. Varshney Daozhang Cai Dong-An Wang |
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| Affiliation: | 1. Center for Stem Cell Biology and Tissue Engineering of Sun Yat-Sen University, Guangzhou 510080, China;2. Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637457, Singapore;3. Key Laboratory of Specially Functional Materials and Advanced Manufacturing Technology, South China University of Technology, Ministry of Education, Guangzhou 510641, China;1. Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA;2. McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA;3. Medicine for Sports and Performing Arts, Department of Health and Sport Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan;4. Fondazione RiMED, Italy;1. Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90025, USA;2. Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;1. Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PT, UK;2. Manchester Institute of Biotechnology and School of Materials, The University of Manchester, Manchester, M1 7DN, UK;3. School of Materials, Faculty of Science and Engineering, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK;4. Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PT, UK;5. NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Grafton St, M13 9WU Manchester, UK;1. Shenzhen Key Laboratory of Anti-Ageing and Regenerative Medicine, Department of Medical Cell Biology and Genetics, Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Medical School, Shenzhen, Guangdong 518060, China;2. Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Guangdong, 518060, China;3. Shenzhen Engineering Laboratory of Orthopaedic Regenerative Technologies, Departments of Orthopaedics, Peking University Shenzhen Hospital, Shenzhen, Guangdong 510086, China;4. The Charles Institute of Dermatology, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland;5. Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA;6. Schools of Dentistry, Engineering and Medicine, University of Michigan, Ann Arbor, MI 48109-1078, USA;7. Shenzhen Anhe Health Sciences Co. Ltd., Longhua District, Shenzhen, China;1. Division of Advanced Prosthodontics, University of California, Los Angeles, CA 90095, USA;2. Department of Bioengineering, University of California, Los Angeles, CA 90095, USA;3. Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA;4. Division of Diagnostic and Surgical Sciences, University of California, Los Angeles, CA 90095, USA;5. Department of Bio and Chemical Engineering, Hongik University, Sejong 339-701, Republic of Korea;6. Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA |
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| Abstract: | Synovium-derived mesenchymal stem cells (SMSC), a novel line of stem cells, are regarded as a promising cell source for cartilage tissue engineering. The goal of this study was to investigate rabbit SMSC coupled with injectable gellan hydrogels for in vitro engineered cartilage. SMSC were isolated from rabbit synovial tissue, amplified to passage 4 in monolayer, and encapsulated in injectable gellan hydrogels, constructs of which were cultured in chondrogenic medium supplemented with TGF-β1, TGF-β3 or BMP-2 for up to 42 days. The quality of the constructs was assessed in terms of cell proliferation and chondrocytic gene/protein expression using WST-1 assay, real-time RT-PCR, biochemical analysis, histology and immunohistochemical analysis. Results indicate that the viability of SMSC in hydrogels treated with TGF-β1, TGF-β3 and BMP-2 remained high at culture time. The constructs formed cartilaginous tissue with the expression of chondrocytic genes (collagen type II, aggrecan, biglycan, SOX 9) and cartilaginous matrix (sulphated glycosaminoglycan and collagen) as early as 21 days in culture. Both TGF-β1 and TGF-β3 treated SMSC-laden hydrogels showed more chondrogenesis compared with BMP-2 treated SMSC-laden hydrogels. It demonstrates that injectable SMSC-laden gels, when treated with TGF-β1, TGF-β3 or BMP-2, are highly competent for in vitro engineered cartilage formation, which lays a foundation for their potential application in clinical cartilage repair. |
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