Bone marrow mesenchymal stem cells with low dose bone morphogenetic protein 2 enhances scaffold-based spinal fusion in a porcine model
Tao Hu
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Department of Spine Surgery, Tongji University School of Medicine, Shanghai East Hospital, Shanghai, China
Search for more papers by this authorCorresponding Author
Ling Liu
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Correspondence
Ling Liu, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 15 Kent Ridge Crescent, E7, #06-03, Singapore 119276, Singapore.
Email: [email protected]
Search for more papers by this authorRaymond Wing Moon Lam
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorSoo Yein Toh
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorSunny Akogwu Abbah
Department of Obstetrics and Gynaecology, Portiuncula University Hospital Ballinasloe, Galway, Ireland
CÚRAM, Centre for Research in Medical Devices, National University of Ireland, Galway, Ireland
Search for more papers by this authorMing Wang
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorAmit Kumarsing Ramruttun
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorKishore Bhakoo
Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
Search for more papers by this authorSimon Cool
Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
Search for more papers by this authorJun Li
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Search for more papers by this authorJames Cho-Hong Goh
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Search for more papers by this authorHee-Kit Wong
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
NUS Tissue Engineering Programme (NUSTEP), Life Sciences Institute, Singapore, Singapore
Search for more papers by this authorTao Hu
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Department of Spine Surgery, Tongji University School of Medicine, Shanghai East Hospital, Shanghai, China
Search for more papers by this authorCorresponding Author
Ling Liu
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Correspondence
Ling Liu, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 15 Kent Ridge Crescent, E7, #06-03, Singapore 119276, Singapore.
Email: [email protected]
Search for more papers by this authorRaymond Wing Moon Lam
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorSoo Yein Toh
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorSunny Akogwu Abbah
Department of Obstetrics and Gynaecology, Portiuncula University Hospital Ballinasloe, Galway, Ireland
CÚRAM, Centre for Research in Medical Devices, National University of Ireland, Galway, Ireland
Search for more papers by this authorMing Wang
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorAmit Kumarsing Ramruttun
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorKishore Bhakoo
Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
Search for more papers by this authorSimon Cool
Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
Search for more papers by this authorJun Li
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Search for more papers by this authorJames Cho-Hong Goh
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Search for more papers by this authorHee-Kit Wong
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
NUS Tissue Engineering Programme (NUSTEP), Life Sciences Institute, Singapore, Singapore
Search for more papers by this authorAbstract
High doses bone morphogenetic protein 2 (BMP-2) have resulted in a series of complications in spinal fusion. We previously established a polyelectrolyte complex (PEC) carrier system that reduces the therapeutic dose of BMP-2 in both rodent and porcine spinal fusion models. This study aimed to evaluate the safety and efficacy of the combination of bone marrow mesenchymal stem cells (BMSCs) and low dose BMP-2 delivered by PEC for bone regeneration in a porcine model of anterior lumbar interbody spinal fusion (ALIF) application. Six Yorkshire pigs underwent a tri-segmental (L2/L3; L3/L4; L4/L5) ALIF in four groups, namely: (a) BMSCs + 25 μg BMP-2/PEC (n = 9), (b) 25 μg BMP-2/PEC (n = 3), (c) BMSCs (n = 3), and (d) 50 μg BMP-2/absorbable collagen sponge (n = 3). Fusion outcomes were evaluated by radiography, biomechanical testing, and histological analysis after 12 weeks. Mean radiographic scores at 12 weeks were 2.7, 2.0, 1.0, and 1.0 for Groups 1 to 4, respectively. μ-CT scanning, biomechanical evaluation, and histological analysis demonstrated solid fusion and successful bone regeneration in Group 1. In contrast, Group 2 showed inferior quality and slow rate of fusion, and Groups 3 and 4 failed to fuse any of the interbody spaces. There was no obvious evidence of seroma formation, implant rejection, or any other complications in all groups. The results suggest that the combination of BMSCs and low dose BMP-2/PEC could further lower down the effective dose of the BMP-2 and be used as a bone graft substitute in the large animal ALIF model.
CONFLICT OF INTEREST
Dr. Hee-Kit Wong reports personal fees from SpineGuard, outside the submitted work. All the other authors certify that neither he nor she, nor any member of his or her immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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| term3260-sup-0001-fig_s1.jpg804 KB | Figure S1 |
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