Antibody-Mediated Osseous Regeneration for Bone Tissue Engineering in Canine Segmental Defects

Among many applications of therapeutic monoclonal antibodies (mAbs), a unique approach for regenerative medicine has entailed antibody-mediated osseous regeneration (AMOR). In an effort to identify a clinically relevant model of craniofacial defect, the present study investigated the efficacy of mAb specific for bone morphogenetic protein- (BMP-) 2 to repair canine segmental mandibular continuity defect model. Accordingly, a 15 mm unilateral segmental defect was created in mandible and fixated with a titanium plate. Anorganic bovine bone mineral with 10% collagen (ABBM-C) was functionalized with 25 μg/mL of either chimeric anti-BMP-2 mAb or isotype-matched mAb (negative control). Recombinant human (rh) BMP-2 served as positive control. Morphometric analyses were performed on computed tomography (CT) and histologic images. Bone densities within healed defect sites at 12 weeks after surgery were 1360.81 ± 10.52 Hounsfield Unit (HU), 1044.27 ± 141.16 HU, and 839.45 ± 179.41 HU, in sites with implanted anti-BMP-2 mAb, rhBMP-2, and isotype mAb groups, respectively. Osteoid bone formation in anti-BMP-2 mAb (42.99% ± 8.67) and rhBMP-2 (48.97% ± 2.96) groups was not significantly different but was higher (p<0.05) than in sites with isotype control mAb (26.8% ± 5.35). In view of the long-term objective of translational application of AMOR in humans, the results of the present study demonstrated the feasibility of AMOR in a large clinically relevant animal model

Mechanical and Chemical Predifferentiation of Mesenchymal Stem Cells Into Cardiomyocytes and Their Effectiveness on Acute Myocardial Infarction

Myocardial infarction is one of the leading causes of death all over the world. Mesenchymal stem cells (MSCs) transplantation has shown a promising potential to recovery of ischemic heart disease due to their capability in differentiating into cardiac cells. However, various investigations have been performed to optimize the efficacy of cardiac cell therapy in recent years. Here, we sought to interrogate the effect of autologous transplantation of undifferentiated and predifferentiated adipose and bone marrow-derived MSCs in a rabbit model of myocardial infarction and also to investigate whether cardiac function could be improved by mechanically induced MSCs via equiaxial cyclic strain. The two sources of MSCs were induced toward cardiomyocyte phenotype using mechanical loading and chemical factors and thereafter injected into the infarcted myocardium of 35 rabbits. Echocardiography and histopathology studies were used to evaluate cardiac function after 2 months. The results demonstrated significant scar size reduction and greater recovery of left ventricle ejection fraction after transplantation of predifferentiated cells, though the differences were not significant when comparing mechanically with chemically predifferentiated MSCs. Thus, although there was no significant improvement in infarcted myocardium between chemically and mechanically predifferentiated MSCs, mechanically induced cells are more preferred due to lack of any chemical intervention and cost reasonableness in their preparation method. Outcomes of this study may be useful for developing future therapeutic strategies, however long-term assessments are still required to further examine their effectiveness. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc