Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma |
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| Authors: | Wei-Hong Chen Hen-Yu Liu Wen-Cheng Lo Shinn-Chih Wu Chau-Hwa Chi Hsueh-Yuan Chang Shih-Hsiang Hsiao Chih-Hsiung Wu Wen-Ta Chiu Bao-Ji Chen Win-Ping Deng |
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| Institution: | 1. Stem Cell Research Center, Taipei Medical University, Taipei, Taiwan, ROC;2. Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan, ROC;3. Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan, ROC;4. Department of Neurosurgery, Taipei Medical University, Taipei, Taiwan, ROC;5. Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan, ROC;6. School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan, ROC;7. School of Pharmacy, College of Medicine, National Taiwan University, Taiwan, ROC;8. Division of General Surgery, Department of Surgery, Taipei Medical University, Taiwan, ROC;9. Department of Neurosurgery, Taipei Medical University–Wan Fang Hospital, Taipei, Taiwan, ROC;10. Cancer Center, Taipei Medical University Hospital, Taipei, Taiwan, ROC;1. AO Research Institute Davos, Davos 7270, Switzerland;2. MIRA Institute for Biomedical Technology and Technical Medicine, Department of Biomaterials Science and Technology, University of Twente, AE Enschede 7500, The Netherlands;3. Department of Orthopaedic Surgery, University of Bern, Bern 3010, Switzerland;4. University of Groningen, University Medical Center Groningen, W.J. Kolff Institute, Department of Biomedical Engineering, AD Groningen 9700, The Netherlands;5. Collaborative Research Partner Annulus Fibrosus Repair Programme, AO Foundation, Davos 7270, Switzerland;1. Department of Neurosurgery, Taipei Medical University Hospital, Taipei, Taiwan, ROC;2. School of Medicine, Taipei Medical University, Taipei, Taiwan, ROC;3. Stem Cell Research Center, Taipei Medical University, Taipei, Taiwan, ROC;4. Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan, ROC;5. Food Industry Research and Development Institute Culture Collection and Research Center, Taiwan, ROC;6. Department of Orthopedic Surgery, The Affiliated Hospital, Guangdong Medical College, Zhanjiang 524001, China;7. College of Oral Medicine, Taipei Medical University, Taipei, Taiwan, ROC;8. Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan, ROC;9. Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA;10. Cancer Center, Taipei Medical University and Hospital, Taipei, Taiwan, ROC;1. Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, Queensland 4072, Australia;2. Mesoblast Ltd, Level 39, 55 Collins Street, Melbourne 3000, Australia;3. School of Biomedical Sciences, University of Queensland, St Lucia, Queensland 4072, Australia;4. Mesenchymal Stem Cell Laboratory, School of Medical Sciences, Faculty of Health Sciences, University of Adelaide, Adelaide, 5005 South Australia, Australia;5. Myeloma Research Laboratory, School of Medical Sciences, Faculty of Health Science, University of Adelaide, Adelaide, South Australia 5000, Australia;6. School of Chemical Engineering, University of Queensland, St. Lucia, Queensland 4072, Australia;7. CSIRO Materials Science and Engineering Division, Clayton, 3168 Victoria, Australia;1. Department of Orthopaedic Surgery, University of Pennsylvania, McKay Orthopaedic Research Laboratory, 36th Street and Hamilton Walk, 424 Stemmler Hall, Philadelphia, PA 19104-6081, USA;2. Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, 3900 Woodland Avenue, Building 21, Room A222, Philadelphia, PA 19104, USA;3. Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania, 220 South 33rd Street, 229 Towne Building, Philadelphia, PA 19104-6315, USA;4. Department of Biomedical Engineering, University of Delaware, 150 Academy Street, Room 161 Colburn Laboratory, Newark, DE 19716 , USA;5. Department of Neurosurgery, University of Pennsylvania, 3400 Spruce Street, 3rd Floor, Silverstein Pavilion, Philadelphia, PA 19104, USA;6. Department of Bioengineering, University of Pennsylvania, 210 South 33rd Street, Suite 240, Skirkanich Hall, Philadelphia, PA 19104-6321, USA;1. Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region;2. Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region;3. Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region |
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| Abstract: | An ex vivo degenerative intervertebral disc (IVD) organ culture system was established for the screening of disc regeneration agents. Its application was demonstrated by a stem cell and growth factor-based therapeutic approach for the amelioration of IVD. An ex vivo culture system using chymopapain to partially digest nucleus proposus tissue was established to mimic human IVD degeneration. This system was then used for the evaluation of different therapeutic regimens including: mesenchymal stem cell derived from eGFP-transgenic porcine (MSC-GFP), platelet-rich plasma (PRP) and MSC-GFP/PRP combined treatment, and confirmed in in vivo animal model. Chondrogenic-specific gene products including Col II and aggrecan were found upregulated and chondrogenic matrix deposition increased, as evident by sustained fluorescent signals over 4 weeks, in the MSC-GFP implanted group. Previously, we demonstrated in vitro stage-specific chondrogenesis of MSC by chondrocytic commitment. These same molecules upregulated for chondrogenesis were also observed in MSC-GFP group. PRP that has been shown to promote nucleus pulposus (NP) regeneration also resulted in significant increased levels of mRNA involved in chondrogenesis and matrices accumulation. The ex vivo IVD regeneration results were repeated and supported by in vivo porcine degenerative system. Moreover, the disc height index (DHI) was significantly increased in both in vivo MSC-GFP and PRP regeneration groups. Unexpectedly, the MSC-GFP/PRP combined therapy demonstrated an inclination towards osteogenesis in ex vivo system. The ex vivo degenerative IVD culture system described in this study could serve as an alternative and more accessible model over large animal model. This system also provides a high-throughput platform for screening therapeutic agents for IVD regeneration. |
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| Keywords: | Intervertebral disc Mesenchymal stem cell Platelet-rich plasma Nucleus pulposus Regeneration |
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