Enhanced human T cell expansion with inverse opal hydrogels

Santos, Fabião; Valderas-Gutiérrez, Julia; Río, Eduardo Pérez Del; Castellote‐Borrell, Miquel; Rodrı́guez, Xavier; Veciana, Jaume; Ratera, Imma; Guasch, Judith

doi:10.1039/d2bm00486k

Cited by 11 publications

(9 citation statements)

References 59 publications

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“…Interestingly, we identified different modulations of a variety of genes; for example, we observed upregulation of the CXCR3 gene, involved in leukocyte trafficking, integrin activation, and cytoskeletal and focal adhesion remodeling (ie, the HCLS1 gene, involved in the migration and homing of CLL cells 11 and prognostic factors 12,13 ). These results also suggest that, for cells usually grown in suspension in vitro, we can obtain a different phenotype in 3D culture; this offers the possibility of recreating the spatial organization and disposition found in tissues in vivo 14,15 (Figure 1). Another important aspect to consider is that cells arranged in monolayers or in suspension receive all the same amounts of oxygen, nutrients, and growth factors, and consequently more cells will be in the same phase of the cell cycle.…”

Section: D Versus 3d Culture: In What They Differmentioning

confidence: 70%

Emerging Strategies in 3D Culture Models for Hematological Cancers

Barozzi

Scielzo

2023

HemaSphere

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In vitro cell cultures are fundamental and necessary tools in cancer research and personalized drug discovery. Currently, most cells are cultured using two-dimensional (2D) methods, and drug testing is mainly performed in animal models. However, new and improved methods that implement three-dimensional (3D) cell-culturing techniques provide compelling evidence that more advanced experiments can be performed, yielding valuable new insights. In 3D cell-culture experiments, the cell environment can be manipulated to mimic the complexity and dynamicity of the human tissue microenvironment, possibly leading to more accurate representations of cell-to-cell interactions, tumor biology, and predictions of drug response. The 3D cell cultures can also potentially provide alternative ways to study hematological cancers and are expected to eventually bridge the gap between 2D cell culture and animal models. The present review provides an overview of the complexity of the lymphoid microenvironment and a summary of the currently used 3D models that aim at recreating it for hematological cancer research. We here dissect the differences and challenges between, and potential advantages of, different culture methods and present our vision of the most promising future strategies in the hematological field.

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Section: D Versus 3d Culture: In What They Differmentioning

confidence: 70%

Emerging Strategies in 3D Culture Models for Hematological Cancers

Barozzi

Scielzo

2023

HemaSphere

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“…Primary human peripheral blood mononuclear cells (PBMCs) were obtained following an established protocol. − In brief, PBMCs were isolated using a density gradient centrifugation with Ficoll from buffy coats supplied by “Banc de Sang i Teixits” (Barcelona, Spain) under the approval of the “Ethics Committee on Animal and Human Experimentation” of the Autonomous University of Barcelona (Nr. : 5099).…”

Section: Methodsmentioning

confidence: 99%

pH-Sensitive Acrylic Terpolymers for the Coating of Orally Administered Drugs Used for Colonic Release

Suárez,

Hoyos,

Castellote-Borrell

et al. 2023

ACS Omega

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Polymeric coatings are a promising option for the development of delivery systems for orally administered drugs. However, the gastrointestinal conditions to which they are subjected, which include low pH and solubility as well as peristaltic movements, can limit their applications. In this work, different formulations of polymeric coatings were produced using pH-sensitive materials consisting of copolymers of methyl acrylate, methyl methacrylate, and methacrylic acid. The polymers were synthesized by the emulsion polymerization technique, obtaining small average particle sizes (56–190 nm), molecular weights between 200,000 and 400,000 g/mol, and a glass transition temperature above 35 °C, which are suitable for film formation at room temperature. Thus, they were assessed as coatings for hydroxypropyl methylcellulose capsules (HPMC) using the immersion method, showing adequate capacity to protect the capsule at gastric pH (pH 1.2) and dissolve at the simulated intestinal pH (pH= 7.2). In particular, the higher the content of the acidic monomer, the higher the release time of the test molecule contained in the acrylic terpolymer-coated HPMC capsules proposed, which was a curcuminoid derivative due to their bright color and potential medical benefits. In addition, a minimum number of immersions was required for coating the HPMC capsules at high acidic concentrations, which further facilitates the delayed release needed for colonic treatment. However, too high proportions of methacrylic acid may result in cytotoxicity issues. Consequently, a biocompatible formulation containing a proportion of methyl acrylate, methyl methacrylate, and methacrylic acid of 7:3:3 is proposed as the most adequate for colonic release. Thus, by chemically modulating the molar percentages of the acrylic monomers, it was possible to obtain tailored acrylic terpolymer coatings with different characteristics and desired properties in order to modulate the release kinetics of an active substance in a colonic environment.

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“…[53] Poly(methyl methacrylate) (PMMA) microbeads were mixed with the PEG-heparin solution and crosslinked; the beads were dissolved to create a hydrogel scaffold with numerous, vacant bubble-like structures called an inverse opal hydrogel. [53] Physiologically, the lymph node is a mesh-like structure that is compartmentalized for lymphatic fluid and different immune cells. [54,55] In this attempt to physically reconstruct the lymph node, authors found that proliferation was significantly enhanced when compared to using Dynabeads alone.…”

Section: Expansionmentioning

confidence: 99%

“…[54,55] In this attempt to physically reconstruct the lymph node, authors found that proliferation was significantly enhanced when compared to using Dynabeads alone. [53] Further, the inverse opal hydrogel allowed T cell differentiation and expansion into many heterogenous cell types such as naïve T cells, central memory T cells, and effector memory T cells. When Dynabeads were co-cultured with T cells in the hydrogel, expansion saw 63% improvement when compared to cells activated in suspension and 34% improvement compared to the bulk hydrogel alone.…”

Section: Expansionmentioning

confidence: 99%

Hydrogel‐Based Strategies to Enhance T‐Cell Performance for Solid Tumor Immunotherapy

Kim

2023

Advanced Therapeutics

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The solid tumor microenvironment presents many challenges for immunotherapy that must be addressed for clinical relevance. This review will highlight research that has attempted to tackle these challenges and summarize recent therapeutic approaches to enhance both native and engineered T cell functions through hydrogel delivery. Different types of hydrogels are presented in this paper and organized based on purpose of the research: activation and expansion, delivery methods, co‐delivery of immunostimulating agents, and overcoming tumor microenvironment barriers. Perspectives in the future of solid cancer immunotherapy are also discussed to share opinion on necessary research for the success in this field.

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Enhanced human T cell expansion with inverse opal hydrogels

Abstract: Lymph node-inspired 3D hydrogels with precisely defined porosity were produced, which improve the state-of-the-art T cell proliferation, a procedure that is especially important for novel cellular immunotherapies.

Cited by 11 publications

References 59 publications

Emerging Strategies in 3D Culture Models for Hematological Cancers

Emerging Strategies in 3D Culture Models for Hematological Cancers

pH-Sensitive Acrylic Terpolymers for the Coating of Orally Administered Drugs Used for Colonic Release

Hydrogel‐Based Strategies to Enhance T‐Cell Performance for Solid Tumor Immunotherapy

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