RESUMEN
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.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Regeneración Ósea/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Animales , Densidad Ósea/efectos de los fármacos , Proteína Morfogenética Ósea 2/metabolismo , Colágeno/metabolismo , Perros , Humanos , Masculino , Mandíbula/efectos de los fármacos , Mandíbula/metabolismo , Proteínas Recombinantes/metabolismo , Ingeniería de Tejidos/métodos , Andamios del Tejido , Titanio/farmacología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
OBJECTIVES: Adult stem cells (ASCs) remain in a slowly cycling/quiescent state under normal physiological conditions, but they can be awakened from this by certain factors, such as injury signals. Previously, our group has shown that dental follicle stem cells (DFSCs) appear to proliferate more rapidly than their non-stem cell counterparts at elevated temperatures. The study described here has aimed to (i) elucidate optimal temperature in which to culture DFSCs, (ii) determine whether elevated temperatures could enhance differentiation capability of DFSCs and (iii) characterize stem cell and osteogenic marker expression of DFSCs at elevated temperatures. MATERIALS AND METHODS: DFSCs obtained from rat first molars were cultured at 37 (control), 38, 39, 40 and 41 ºC. Cell proliferation was evaluated by Alamar blue reduction assay and mean numbers of viable dissociated cells. Osteogenic differentiation was evaluated after 7 or 14 days osteogenic induction. Expression of selected marker genes was also assessed during proliferation and differentiation of the cells. RESULTS: Increased cell proliferation was seen at heat-stress temperatures of 38º, 39º and 40 ºC. DFSCs revealed maximal osteogenesis when cultured at 39 and 40 ºC. Moreover, some stem cell and osteogensis-associated markers had elevated expression in heat-stress conditions. CONCLUSIONS: Under determined heat-stress conditions, DFSCs increased their proliferation, osteogenic differentiation and expression of some marker genes. Thus, it is likely that elevated temperature could serve as a factor to activate adult stem cells.
Asunto(s)
Diferenciación Celular , Saco Dental/citología , Calor , Células Madre/citología , Estrés Fisiológico , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Animales , Proteína Morfogenética Ósea 3/genética , Proteína Morfogenética Ósea 3/metabolismo , Proliferación Celular , Células Cultivadas , Colágeno Tipo IX/genética , Colágeno Tipo IX/metabolismo , Expresión Génica , Osteogénesis , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Ratas , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Células Madre/metabolismoRESUMEN
BACKGROUND: Concept of e-readiness is used in many areas such as e-business, e-commerce, e-government, and e-banking. In terms of healthcare, e-readiness is a rather new concept, and is propounded under the title of E-healthcare. E-health readiness refers to the readiness of communities and healthcare institutions for the expected changes brought by programs related to Information and Communications Technology (lCT). The present research is conducted aiming at designing E-health Readiness Assessment Framework (EHRAF) in Iran. METHODS: The e-health readiness assessment framework was designed based on reviewing literature on e-readiness assessment models and opinions of ICT and health experts. In the next step, Delphi method was used to develop and test the designed framework. Three questionnaires developed to test and modify the model while determining weights of the indices; afterward they were either sent to experts through email or delivered to them in face. RESULTS: The designed framework approved with 4 dimensions, 11 constituents and 58 indices. Technical readiness had the highest importance coefficient (0.256099), and the other dimensions were of the next levels of coefficient importance: core readiness (0.25520), social communication readiness (0.244658), and engagement readiness (0.244039). CONCLUSION: The framework presents the movement route and investment priorities in e-health in Iran. The proposed framework is a good instrument for measuring the e-readiness in health centers in Iran, and for identifying strengths and weaknesses of these centers to access ICT and its implementation for more effectiveness and for analyzing digital divide between them, as well.
