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Transplantation of human mesenchymal stem cells in a non-autogenous setting for bone regeneration in a rabbit critical-size defect model
Authors:P. Niemeyer  K. Szalay  R. Luginbühl  N.P. Südkamp  P. Kasten
Affiliation:1. Department of Orthopedic Surgery and Traumatology, Freiburg University Hospital, Germany;2. Department of Orthopedic Surgery, Heidelberg University Hospital, Germany;3. Dr. h.c. Robert Mathys Foundation, Bettlach, Switzerland;4. Department of Orthopedic Surgery, Dresden University Hospital, University of Dresden, Fetscherstr. 74, 01307 Dresden, Germany;1. Department of Oral and Maxillofacial Prosthodontics and Oral Implantology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan;2. Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, Aichi, Japan;3. Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö, Sweden;4. Division of Radiology, Department of Maxillofacial Diagnostic Science, Kanagawa Dental College, Yokosuka, Japan;5. Department of Periodontology & Oral Implantology, Dental School, Faculty of Medicine and Health Sciences, University of Ghent, Ghent, Belgium;6. Department of Biomaterials and Biomimetics, New York University College of Dentistry, NY, USA;1. The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China;2. Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China;3. Engineering Research Center for Biomaterials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China;4. Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, PR China;1. Department of Orthopedic Surgery, Xijing Hospital, The Fourth Military Medical University, 17 West Changle Road, Xi''an, China;2. Department of Orthopaedics & Traumatology, Nanfang Hospital, Nanfang Medical University, Guangzhou, China;3. Collage of Science, Engineering University of Air Force, Xi''an, China;1. Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi’an 710032, China;2. Department of Stomatology, PLA 252 Hospital, Baoding 071000, China;3. Department of Orthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;4. Department of Oral and Maxillofacial Surgery, Lanzhou General Hospital, Lanzhou Command of PLA, Lanzhou 730000, China;1. Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney 2006, Australia;2. University of Ballarat B, Victoria 3350, Australia;3. Flinders University, Adelaide 5001, Australia;4. Adelaide Microscopy, The University of Adelaide, South Australia 5005, Australia;1. Department of Trauma-, Hand- and Reconstructive Surgery, Hospital of the Goethe- University, Frankfurt/Main, Germany;2. Heraeus Medical GmbH, Wehrheim, Germany
Abstract:Human mesenchymal stem cells (hMSC) represent an attractive cell population for tissue engineering purposes. Furthermore, hMSC are described as immune privileged, and non-autogenous application seems possible. The current study examines the regeneration potential of hMSC after xenogenic transplantation compared with autogenous rabbit MSC in a critical-size bone defect. After isolation, hMSC and rabbit MSC were seeded on calcium-deficient hydroxyapatite (CDHA) and transplanted into a radial critical-size defect of New Zealand white rabbits. Defects were filled with a CDHA scaffold seeded with autogenous rabbit MSC, CDHA seeded with xenogenic hMSC or unseeded CDHA. An empty defect served as control group. Animals were sacrificed after 3 months. Evaluation was performed using radiography, micro-computed tomography (μ-CT) and histology. In addition, a non-destructive four-point-bending test was performed in order to evaluate biomechanical stiffness. While autogenous MSC seeded on CDHA led to increased healing of critical-size bone defects from radiological (μ-CT; p = 0.009) and histological (p = 0.048) perspectives compared with unloaded CDHA, it was not possible to demonstrate analogous effects for the xenogenic transplantation of hMSC. The xenogenic treatment group displayed inferior results in all parameters compared with the autogenous MSC treatment group (histology p = 0.041; μ-CT p = 0.006; biomechanical testing p = 0.017). Nevertheless, no local or systemic inflammatory response resulting from xenogenic transplantation was observed. While previous papers suggest the use of non-autogenous hMSC cells for tissue engineering purposes, the present results show inferior clinical results from transplantation of hMSC in a xenogenic setting compared with autogenous MSC.
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