30 research outputs found
Preparation of Porous Biphasic Calcium Phosphate-Gelatin Nanocomposite for Bone Tissue Engineering
Effect of Freezing and Thawing Process on Betamethasone Acetate Release from Polyvinyl Alcohol Nanospheres
Genetically engineered T cells bearing chimeric nanoconstructed receptors harboring TAG-72-specific camelid single domain antibodies as targeting agents
International audienceDespite the preclinical success of adoptive therapy with T cells bearing chimeric nanoconstructed antigen receptors (CARs), certain limitations of this therapeutic approach such as the immunogenicity of the antigen binding domain, the emergence of tumor cell escape variants and the blocking capacity of soluble antigen still remain. Here, we address these issues using a novel CAR binding moiety based on the oligoclonal camelid single domain antibodies. A unique set of 13 single domain antibodies were selected from an immunized camel phage library based on their target specificity and binding affinity. A combination of these single domain antibodies was used to generate four tumor associated glycoprotein (TAG-72)-specific CARs harboring an identical antigen binding site, but with different signaling and spacer domains. Although all four CARs were functionally active against the TAG-72 expressing tumor cells, the combination of CD3Ī¶, OX40, CD28 as well as the CH3-CH2-hinge-hinge domains most efficiently triggered T cell activation. Importantly, CAR mediated functions were not blocked by the soluble TAG-72 antigen at a supraphysiological concentration. Our approach may have the potential to reverse multiple tumor immune evasion mechanisms, avoid CAR immunogenicity, and overcome problems in cancer gene therapy with engineered nanoconstructs
Surface modification of silicone tubes by functional carboxyl and amine, but not peroxide groups followed by collagen immobilization improves endothelial cell stability and functionality
Surface modification by functional groups promotes endothelialization in biohybrid artificial lungs, but whether it affects endothelial cell stability under fluid shear stress, and the release of anti-thrombotic factors, e.g. nitric oxide (NO), is unknown. We aimed to test whether surface-modified silicone tubes containing different functional groups, but similar wettability, improve collagen immobilization, endothelialization, cell stability and cell-mediated NO-release. Peroxide, carboxyl, and amine-groups increased collagen immobilization (41-76%). Only amine-groups increased ultimate tensile strength (2-fold). Peroxide and amine enhanced (1.5-2.5āfold), but carboxyl-groups decreased (2.9-fold) endothelial cell number after 6ād. After collagen immobilization, cell numbers were enhanced by all group-modifications (2.8-3.8āfold). Cells were stable under 1āh-fluid shear stress on amine, but not carboxyl or peroxide-group-modified silicone (>50% cell detachment), while cells were also stable on carboxyl-group-modified silicone with immobilized collagen. NO-release was increased by peroxide and amine (1.1-1.7āfold), but decreased by carboxyl-group-modification (9.8-fold), while it increased by all group-modifications after collagen immobilization (1.8-2.8āfold). Only the amine-group-modification changed silicone stiffness and transparency. In conclusion, silicone-surface modification of blood-contacting parts of artificial lungs with carboxyl and amine, but not peroxide-groups followed by collagen immobilization allows the formation of a stable functional endothelial cell layer. Amine-group-modification seems undesirable since it affected silicone's physical properties
EFFECTS OF SHORT-TERM CYCLIC HYDROSTATIC PRESSURE ON INITIATING AND ENHANCING THE EXPRESSION OF CHONDROGENIC GENES IN HUMAN ADIPOSE-DERIVED MESENCHYMAL STEM CELLS
Cell-Imprinted Substrates Direct the Fate of Stem Cells
Smart nanoenvironments were obtained by cell-imprinted substrates based on mature and dedifferentiated chondrocytes as templates. Rabbit adipose derived mesenchymal stem cells (ADSCs) seeded on these cell-imprinted substrates were driven to adopt the specific shape (as determined in terms of cell morphology) and molecular characteristics (as determined in terms of gene expression) of the cell types which had been used as template for the cell-imprinting. This method might pave the way for a reliable, efficient, and cheap way of controlling stem cell differentiation. Data also suggest that besides residual cellular fragments, which are presented on the template surface, the imprinted topography of the templates plays a role in the differentiation of the stem cells
Physiological Temperature Has a Crucial Role in Amyloid Beta in the Absence and Presence of Hydrophobic and Hydrophilic Nanoparticles
Amyloid beta fibrillation can lead to major disorder
of neurons
processes and is associated with several neuronal diseases (e.g.,
Alzheimerās disease). We report here an importance of slight
temperature changes, in the physiological range (35ā42 Ā°C),
on the amyloid fibrillation process in the presence and absence of
hydrophilic (silica) and hydrophobic (polystyrene) nanoparticles (NPs).
The results highlight the fact that slight increases in temperature
can induce inhibitory and acceleratory effects of hydrophobic and
hydrophilic NPs on the fibrillation process, respectively. Using further
in vivo considerations, the outcomes of this study can be used for
considerable modifications on the current diagnosis and treatment
approaches in amyloid-involved diseases