Artificial 3D Culture Systems for T Cell Expansion

Abstract

Adoptive cell therapy, i.e., the extraction, manipulation, and administration of ex vivo generated autologous T cells to patients, is an emerging alternative to regular procedures in cancer treatment. Nevertheless, these personalized treatments require laborious and expensive laboratory procedures that should be alleviated to enable their incorporation into the clinics. With the objective to improve the ex vivo expansion of large amount of specific T cells, we propose the use of three-dimensional (3D) structures during their activation with artificial antigen-presenting cells, thus resembling the natural environment of the secondary lymphoid organs. Thus, the activation, proliferation, and differentiation of T cells have been analyzed when cultured in the presence of two 3D systems, Matrigel and a 3D polystyrene scaffold, showing an increase in cell proliferation compared to standard suspension systems.

High-Throughput Cell Motility Studies on Surface-Bound Protein Nanoparticles with Diverse Structural and Compositional Characteristics

“…External factors, provided by the extracellular matrix (ECM), operate at every stage of the movement cycle, stabilizing protrusions and maintaining the direction of migration . Thus, cell shape and mobility are governed by the dimensionality of surface decoration (i.e., three-dimensional, two-dimensional (2D), or one-dimensional in the case of a single fiber of collagen), − density and orientation of the ECM ligands (i.e., nanoscale or microscale structures of the ECM), − and stiffness (i.e., mechanical properties of the substrate) . Although many efforts have been made to reproduce in vitro the complex aspects of physiological conditions, further advancements in nanofabrication and synthetic self-assembly are still needed .…”

Fibroblasts upregulate expression of adhesion molecules and promote lymphocyte retention in 3D fibroin/gelatin scaffolds

“…The pore size of 3D scaffolds comprised of different materials used in this study was comparable, ranging from 200 μm in diameter for 3D polystyrene scaffolds to 220 ± 65 μm and 250 ± 80 μm for fibroin and fibroin/gelatin scaffolds, respectively. At the same time, the mechanical stiffness was different for the type of materials used, among which the most rigid was 3D polystyrene with shear modulus ~ 3 × 10 6 kPa [ 63 ], compared to 9.0 ± 1.6 kPa for fibroin/gelatin and at 5.9 ± 1.1 kPa for fibroin. Nevertheless, these differences in rigidness between fibroin and F/G-scaffolds did not significantly affect expression of adhesion molecules, since ICAM-1 expression was highly upregulated in both types of scaffolds, suggesting a stronger contribution from the fibroin itself, rather than from the differences in physical properties of bioengineered materials.…”

At the Intersection of Biomaterials and Gene Therapy: Progress in Non-viral Delivery of Nucleic Acids

“…Besides the use of NP systems, 3D scaffolds have also been developed which can be used as implants at tumor sites. These systems have included commercial Matrigel and polystyrene scaffolds (Pérez Del Río et al, 2018), mesoporous silica microrods with supported lipid bilayer composites (Cheung et al, 2018), 3D-printed polycaprolactone lattices (Delalat et al, 2017), alginate scaffolds (Stephan et al, 2014) and injectable polyisocyanopeptide and PEGylated chitosan hydrogels (Tsao et al, 2014; Weiden et al, 2018a). With such broad possibilities, the versatility of biomaterials to design biomimetic systems to effectively expand T-cells is evident.…”