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Adipose-derived stem cells alleviate osteoporosis by enchancing osteogenesis and inhibiting adipogenesis in a rabbit model
Institution:1. Department of Plastic and Reconstructive Surgery, Shanghai Tenth People''s Hospital, Tongji University, Shanghai, PR China;2. Department of Orthopedic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China;3. The Central Laboratory of Shanghai Tenth People''s Hospital, Tongji University, Shanghai, PR China;1. Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan;2. Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan;3. Department of Orthopaedic, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan;1. Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India;2. Division of Endocrinology, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India;3. Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India;1. Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India;2. Endocrinology Division, CSIR-Central Drug Research Institute, (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India;1. Bone & Joint Research Group, Human Development & Health, Institute of Developmental Sciences, University of Southampton, Southampton, UK;2. The Wolfson Centre for Stem Cells, Tissue Engineering & Modelling (STEM), School of Pharmacy, University of Nottingham, Nottingham, UK;3. Department of Materials, Imperial College London, London, UK;4. Institute for Biomedical Engineering, Imperial College London, London, UK;5. Department of Bioengineering, Imperial College London, London, UK;6. Institute of Polymer Science & Technology, CSIC and CIBER-BBN, Madrid, Spain;7. Institute for Science and Technology in Medicine, School of Medicine, Keele University, Keele, UK;1. Tissue Engineering and Regenerative Medicine Laboratory, Advance Center of Research in Biomedical Sciences/King Edward Medical University/Mayo Hospital, Lahore, Pakistan;2. Department of Immunobiology, College of Medicine, the University of Arizona, Tucson, Arizona, USA;1. Institute for Clinical and Experimental Medicine, Prague, Czech Republic;2. Institute of Experimental Medicine, Czech Academy of Science, Prague, Czech Republic;3. Diabetes Centre, Tameside Hospital NHS Foundation Trust and University of Manchester, Lancashire, United Kingdom
Abstract:Background aimsOsteoporosis (OP) is characterized by a reduction in bone quality, which is associated with inadequacies in bone marrow mesenchymal stromal cells (BMSCs). As an alternative cell source to BMSCs, adipose-derived stem cells (ASCs) have been investigated for bone repair because of their osteogenic potential and self-renewal capability. Nevertheless, whether autologous ASCs can be used to promote bone regeneration under osteoporotic conditions has not been elucidated.MethodsThe OP rabbit model was established by means of bilateral ovariectomy (OVX). Both BMSCs and ASCs were harvested from OVX rabbits and expanded in vitro. The effects of osteogenic-induced ASCs on the in vitro adipogenic and osteogenic capabilities of BMSCs were evaluated. Autologous ASCs were then encapsulated by calcium alginate gel and transplanted into the distal femurs of OVX rabbits (n = 12). Hydrogel without loading cells was injected into the contralateral femurs as a control. Animals were killed for investigation at 12 weeks after transplantation.ResultsOsteogenic-induced ASCs were able to promote osteogenesis and inhibit adipogenesis of osteoporotic BMSCs through activation of the bone morphogenetic protein 2/bone morphogenetic protein receptor type IB signal pathway. Local bone mineral density began to increase at 8 weeks after ASC transplantation (P < 0.05). At 12 weeks, micro–computed tomography and histological evaluation revealed more new bone formation in the cell-treated femurs than in the control group (P < 0.05).ConclusionsThis study demonstrated that ASCs could stimulate proliferation and osteogenic differentiation of BMSCs in vitro and enhance bone regeneration in vivo, which suggests that autologous osteogenic-induced ASCs might be useful to alleviate OP temporally.
Keywords:adipose-derived stem cells  alginate  bone regeneration  osteoporosis  rabbit  tissue engineering
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