ABSTRACT
Carbon nanotubes have been proposed as fillers to reinforce polymeric biomaterials for the strengthening of their structural integrity to achieve better biomechanical properties. In this study, a new polymeric composite material was introduced by incorporating various low concentrations of multiwalled carbon nanotubes (MWCNTs) into chitosan (CS), aiming at achieving a novel composite biomaterial with superior mechanical and biological properties compared to neat CS, in order to be used in cardiovascular tissue engineering applications. Both mechanical and biological characteristics in contact with the two relevant cell types (endothelial cells and vascular myofibroblasts) were studied. Regarding the mechanical behavior of MWCNT reinforced CS (MWCNT/CS), 5 and 10 % concentrations of MWCNTs enhanced the mechanical behavior of CS, with that of 5 % exhibiting a superior mechanical strength compared to 10 % concentration and neat CS. Regarding biological properties, MWCNT/CS best supported proliferation of endothelial and myofibroblast cells, MWCNTs and MWCNT/CS caused no apoptosis and were not toxic of the examined cell types. Conclusively, the new material could be suitable for tissue engineering (TE) and particularly for cardiovascular TE applications.
Subject(s)
Biocompatible Materials/chemistry , Carotid Arteries/pathology , Chitosan/chemistry , Nanotubes, Carbon/chemistry , Tissue Engineering/methods , Animals , Apoptosis , Biomechanical Phenomena , Cardiovascular System/drug effects , Cell Proliferation , Elasticity , Endothelial Cells/cytology , Endothelial Cells/drug effects , Materials Testing , Myofibroblasts/cytology , Myofibroblasts/drug effects , Polymers/chemistry , Sheep , Stress, MechanicalABSTRACT
AIMS: Trophoblast fusion in the placenta is prerequisite to successful pregnancy and the pathological conditions related to it. The presence of syncytin-1, is not sufficient to explain the complete event and ADAM12 is a major co-player candidate. Via differential splicing, the ADAM12 gene produces a short and a long form, being the ADAM12-S and the ADAM12-L respectively. METHODS AND RESULTS: We investigated the localisation of both variants in the human placenta using whole mount in situ hybridisation, immunohistochemistry and Northern blotting in 1st (n=8) and 3rd (n=8) trimester placentae and in the case of NB in several cell lines. In Northern blotting, 1st and 3rd trimester placentae were positive for the ADAM12-S and Bewo, 293HEK, JAR, leucocytes, macrophages, 1st and 3rd trimester placentae were positive for ADAM12-L. In whole mount in situ hybridisation, the 1st and 3rd trimester placental syncytium was positive for both variants. In immunohistochemistry, ADAM12-L localised in the cytotrophoblast of both 1st and 3rd trimester placentae, while ADAM12-S localised in the complete syncytium, often including the cytotrophoblast. CONCLUSION: The different localisation of ADAM12-S and ADAM12-L indicates a possible different role making ADAM12-L a candidate for the fusion event, while the syncytial localisation of the ADAM12-S makes it a candidate for cell-cell and cell-matrix interactions between the placental syncytium and the maternal interface.
Subject(s)
ADAM Proteins/genetics , Membrane Proteins/genetics , Placenta/physiology , RNA, Messenger/genetics , ADAM12 Protein , Female , Humans , Pregnancy , Protein Isoforms/genetics , Tissue DistributionSubject(s)
Cell Differentiation , Intercellular Signaling Peptides and Proteins/metabolism , Placentation , Trophoblasts/cytology , Trophoblasts/metabolism , ADAM Proteins/metabolism , ADAM12 Protein , Animals , Co-Repressor Proteins , Cyclin-Dependent Kinase Inhibitor p57/metabolism , Female , Gene Products, env/metabolism , Humans , Membrane Proteins/metabolism , Mice , Placenta/cytology , Placenta/metabolism , Pre-Eclampsia/etiology , Pre-Eclampsia/metabolism , Pregnancy , Pregnancy Proteins/metabolism , Proteins/metabolism , Signal Transduction , Smad Proteins/metabolism , Trophoblasts/drug effects , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Up-Regulation , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-1/metabolismABSTRACT
Syncytin is a membrane protein derived from the envelope gene of an endogenous retrovirus of the HERV-W family. The gene appears to be almost exclusively expressed in placenta; the protein was found in particular in syncytiotrophoblast. After transfection into various cell types it has proven to be a very fusogenic protein, inducing the formation of syncytia. Therefore, the question rises as to whether syncytin is responsible for the fusion process of villous cytotrophoblast into syncytiotrophoblast in vivo. If so, how is this fusion process regulated if syncytin is found all over the syncytiotrophoblast? Can this process be regulated through local or temporal changes in syncytin expression, or is syncytin merely one factor in a cascade of events leading to fusion limited at some other level? This review will try to summarize the published data on the regulation of fusion in trophoblast models as well as on the localization and regulation of syncytin expression and of its presumed receptors. Assuming that syncytin is the key factor inducing trophoblast fusion, a number of models will be presented by which syncytin and/or its receptors might regulate this process. In some of the hypotheses proposed, local coexpression of syncytin and receptor, leading to blocking of one factor by the other, is of functional relevance.
Subject(s)
Gene Products, env/physiology , Pregnancy Proteins/physiology , Trophoblasts/cytology , Trophoblasts/physiology , Amino Acid Transport System ASC/genetics , Amino Acid Transport System ASC/metabolism , Animals , Cell Fusion , Female , Gene Expression Regulation, Developmental , Humans , Minor Histocompatibility Antigens , Models, Biological , Placenta/physiology , Pregnancy , Retroviridae/physiology , Viral Envelope Proteins/metabolismABSTRACT
A 25-year-old female patient presented with an isolated cervical lymph node enlargement several months after having returned from Spain and Latin America. She had no other signs or symptoms of disease. Leishmania infantum/chagasi was identified as the causative agent. With extended travel activities localized lymph node enlargement due to leishmanial infection should be included in the differential diagnosis of lymphadenopathy of unknown origin.
