J Oral Maxillofac Surg 70:e193-e203, 2012 Adipose-Derived Mesenchymal Stem Cells Enhance Healing of Mandibular Defects in the Ramus of Swine Shanna M. Wilson, MS,* Michael S. Goldwasser, MD, DDS,† Sherrie G. Clark, PhD,‡ Elisa Monaco, PhD,§ Massimo Bionaz, PhD, Walter L. Hurley, PhD,¶ Sandra Rodriguez-Zas, PhD,# Liang Feng, MS,** Zaneta Dymon, BS,†† and Matthew B. Wheeler, PhD‡‡ Purpose: This study investigated the effect of adipose-derived mesenchymal stem cells (ASCs) injected locally or systemically on the bone regeneration of a 10-mm-diameter cylindrical noncritical-size defect in the ramus of the pig mandible. Materials and Methods: Fifteen Yorkshire pigs, weighing 60 to 80 kg, received bilateral 10-mm- diameter cylindrical surgical defects in each ramus of the mandible. Pigs received 1) a direct injection into the defect of 2.5 million carboxy-fluorescein diacetate succinimidyl ester-labeled ASCs from 1 of 2 pig donors (n = 6); 2) an ear vein injection of 5 million carboxy-fluorescein diacetate succinimidyl ester-labeled ASCs from 1 of 2 pig donors (n = 6); or 3) an ear vein injection of culture Dulbecco’s Modified Eagle’s Medium without stem cells (control; n = 3). Pigs from each treatment were sacrificed at 1 hour, 2 weeks, or 4 weeks after surgery. Healing of the defect was evaluated by dual-energy x-ray absorptiometry, micro-computed tomography, fluorescent microscopy, and histology. Results: Bone healing was accelerated in the ASC-injected treatment groups at 2 and 4 weeks after surgery compared with the control pigs. Conclusions: Results from this animal model provide evidence that the injection of ASC locally into a bone defect or systemically can accelerate the healing of bone. © 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:e193-e203, 2012 The treatment of fracture and segmental bone defects is a common procedure in orthopedic surgery in which bone augmentation is frequently essential. There is increased interest in using tissue-engineering strategies to increase bone repair because of the lim- ited supply of materials, the associated morbidity of autologous bone grafts, and the limited osteoinduc- tive potential of allograft bone. The use of stem cells for bone repair/regenera- tion holds great promise. There are several exam- ples of the successful use of bone marrow-derived stem cells (BMSCs) in tissue-engineering applica- tions and disease treatments such as cartilage re- pair, heart diseases, and osteogenesis imperfecta. 1-4 BMSCs are an effective therapeutic approach in clinically challenging scenarios such as fracture Received from the University of Illinois, Urbana, IL. *Graduate Student, Department of Animal Sciences. †Professor, Institute for Genomic Biology. ‡Associate Professor, Department of Veterinary Clinical Medi- cine. §Post-Doctoral Fellow, Department of Animal Sciences. Post-Doctoral Fellow, Department of Animal Sciences and Insti- tute for Genomic Biology. ¶Professor, Department of Animal Sciences. #Professor, Department of Animal Sciences. **Graduate Student, Department of Mechanical Science and En- gineering. ††Undergraduate Student, Department of Animal Sciences. ‡‡Professor, Departments of Animal Sciences and Veterinary Clinical Medicine and Institute for Genomic Biology. Address correspondence and reprint requests to Dr Wheeler: Department of Animal Sciences and Institute for Genomic Biology, University of Illinois, 1207 West Gregory Drive, Urbana, IL 61801; e-mail: mbwheele@illinois.edu © 2012 American Association of Oral and Maxillofacial Surgeons 0278-2391/12/7003-0$36.00/0 doi:10.1016/j.joms.2011.10.029 e193