scholarly journals Lymph node follicle formation and vaccination responses reconstituted in vitro in a human Organ Chip

2019 ◽  
Author(s):  
Girija Goyal ◽  
Bruce Bausk ◽  
Pranav Prabhala ◽  
Liangxia Xie ◽  
Danielle Curran ◽  
...  
Keyword(s):  
Lymph Node ◽  
Plasma Cell ◽  
Self Assembly ◽  
Immune Cell ◽  
Cytidine Deaminase ◽  
Cell Formation ◽  
Three Dimensional ◽  
Human Organ ◽  
Vaccine Responses

ABSTRACTCandidate vaccines and immunotherapeutic drugs often fail in clinical trials as human lymph node (LN) physiology is not faithfully modeled in animal models or immune cell cultures. Here we describe a microfluidic Organ Chip culture device that supports self-assembly of human blood-derived B and T lymphocytes into three-dimensional (3D), germinal center-like lymphoid follicles (LFs) containing Activation-Induced Cytidine Deaminase (AID) expressing lymphocytes. These microengineered LFs support plasma cell differentiation upon activation with IL-4 and CD40 agonistic antibody (AB) or inactivated S. aureus Cowan I (SAC). Immunization of the human LN chip with a quadrivalent split virion influenza vaccine resulted in plasma cell formation, viral strain-specific anti-hemagglutinin immunoglobulin G (IgG) production, and a secreted cytokine profile that recapitulates serum responses of vaccinated humans. Thus, the human LN chip may provide a new tool to study human immune reactions, evaluate vaccine responses, and validate the efficacies and toxicities of immunotherapies in vitro.

scholarly journals An Individual Patient's “Body” on Chips—How Organismoid Theory Can Translate Into Your Personal Precision Therapy Approach

2021 ◽  
Vol 8 ◽  
Author(s):  
Uwe Marx ◽  
Enrico Accastelli ◽  
Rhiannon David ◽  
Hendrik Erfurth ◽  
Leopold Koenig ◽  
...  
Keyword(s):  
Human Body ◽  
Self Assembly ◽  
Three Dimensional ◽  
Disease Process ◽  
Egg Cell ◽  
Human Stem Cells ◽  
Human Organ ◽  
Cell Therapies ◽  
Precision Therapy

The first concepts for reproducing human systemic organismal biology in vitro were developed over 12 years ago. Such concepts, then called human- or body-on-a-chip, claimed that microphysiological systems would become the relevant technology platform emulating the physiology and morphology of human organisms at the smallest biologically acceptable scale in vitro and, therefore, would enable the selection of personalized therapies for any patient at unprecedented precision. Meanwhile, the first human organoids—stem cell-derived complex three-dimensional organ models that expand and self-organize in vitro—have proven that in vitro self-assembly of minute premature human organ-like structures is feasible, once the respective stimuli of ontogenesis are provided to human stem cells. Such premature organoids can precisely reflect a number of distinct physiological and pathophysiological features of their respective counterparts in the human body. We now develop the human-on-a-chip concepts of the past into an organismoid theory. We describe the current concept and principles to create a series of organismoids—minute, mindless and emotion-free physiological in vitro equivalents of an individual's mature human body—by an artificially short process of morphogenetic self-assembly mimicking an individual's ontogenesis from egg cell to sexually mature organism. Subsequently, we provide the concept and principles to maintain such an individual's set of organismoids at a self-sustained functional healthy homeostasis over very long time frames in vitro. Principles how to perturb a subset of healthy organismoids by means of the natural or artificial induction of diseases are enrolled to emulate an individual's disease process. Finally, we discuss using such series of healthy and perturbed organismoids in predictively selecting, scheduling and dosing an individual patient's personalized therapy or medicine precisely. The potential impact of the organismoid theory on our healthcare system generally and the rapid adoption of disruptive personalized T-cell therapies particularly is highlighted.

scholarly journals A Rapid Self-Assembly Peptide Hydrogel for Recruitment and Activation of Immune Cells

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 419
Author(s):  
Ruyue Luo ◽  
Yuan Wan ◽  
Xinyi Luo ◽  
Guicen Liu ◽  
Zhaoxu Li ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Dendritic Cells ◽  
Self Assembly ◽  
Immune Cell ◽  
Three Dimensional ◽  
Hydrophobic Surface ◽  
Inhibitory Effect ◽  
Blue Staining ◽  
Peptide Hydrogel

Self-assembly peptide nanotechnology has attracted much attention due to its regular and orderly structure and diverse functions. Most of the existing self-assembly peptides can form aggregates with specific structures only under specific conditions and their assembly time is relatively long. They have good biocompatibility but no immunogenicity. To optimize it, a self-assembly peptide named DRF3 was designed. It contains a hydrophilic and hydrophobic surface, using two N-terminal arginines, leucine, and two c-terminal aspartate and glutamic acid. Meanwhile, the c-terminal of the peptide was amidated, so that peptide segments were interconnected to increase diversity. Its characterization, biocompatibility, controlled release effect on antigen, immune cell recruitment ability, and antitumor properties were examined here. Congo red/aniline blue staining revealed that peptide hydrogel DRF3 could be immediately gelled in PBS. The stable β-sheet secondary structure of DRF3 was confirmed by circular dichroism spectrum and IR spectra. The observation results of cryo-scanning electron microscopy, transmission electron microscopy, and atomic force microscopy demonstrated that DRF3 formed nanotubule-like and vesicular structures in PBS, and these structures interlaced with each other to form ordered three-dimensional nanofiber structures. Meanwhile, DRF3 showed excellent biocompatibility, could sustainably and slowly release antigens, recruit dendritic cells and promote the maturation of dendritic cells (DCs) in vitro. In addition, DRF3 has a strong inhibitory effect on clear renal cell carcinoma (786-0). These results provide a reliable basis for the application of peptide hydrogels in biomedical and preclinical trials.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

scholarly journals In vitro Self-Assembly of Human Pericyte-Supported Endothelial Microvessels in Three-Dimensional Coculture: A Simple Model for Interrogating Endothelial-Pericyte Interactions

2013 ◽  
Vol 50 (4) ◽  
pp. 324-331 ◽  
Author(s):  
J.P. Waters ◽  
M.S. Kluger ◽  
M. Graham ◽  
W.G. Chang ◽  
J.R. Bradley ◽  
...  
Keyword(s):  
Simple Model ◽  
Self Assembly ◽  
Three Dimensional

scholarly journals Cyclosporine A Directly Affects Human and Mouse B cell Migration in vitro by Disrupting a HIF-1α Dependent, O2 Sensing, Molecular Switch

2019 ◽  
Author(s):  
Shannon P Hilchey ◽  
Mukta G Palshikar ◽  
Dongmei Li ◽  
Jessica Garigen ◽  
Valantina Cipolla ◽  
...  
Keyword(s):  
Lymph Node ◽  
Cyclosporine A ◽  
Adaptive Immune Response ◽  
Post Translational Modification ◽  
Low Oxygen ◽  
Modification System ◽  
Vaccine Responses ◽  
Hypoxic Conditions ◽  
Calcineurin Inhibition

AbstractBackgroundHypoxia is a potent molecular signal for cellular metabolism, mitochondrial function, and migration. Conditions of low oxygen tension trigger regulatory cascades mediated via the highly conserved HIF-1α post-translational modification system. In the adaptive immune response, B cells (Bc) are activated and differentiate under hypoxic conditions within lymph node germinal centers, and subsequently migrate to other compartments. During migration, they traverse through changing oxygen levels, ranging from 1-5% in the lymph node to 5-13% in the peripheral blood. Interestingly, the calcineurin inhibitor cyclosporine A is known to stimulate prolyl hydroxylase activity, resulting in HIF-1α destabilization and may alter Bc responses directly. Over 60% of patients taking calcineurin immunosuppressant medications have hypo-gammaglobulinemia and poor vaccine responses, putting them at high risk of infection with significantly increased morbidity and mortality.ResultsWe demonstrate that O2 tension is a previously unrecognized Bc regulatory switch, altering CXCR4 chemokine receptor signaling in activated Bc through HIF-1α expression and controlling critical aspects of Bc migration. Our data demonstrate that calcineurin inhibition hinders this O2 regulatory switch in primary human Bc.ConclusionThis previously unrecognized effect of calcineurin inhibition directly on human Bc has significant and direct clinical implications.

scholarly journals A vascularized 3D model of the human pancreatic islet for ex vivo study of immune cell-islet interaction

2021 ◽  
Author(s):  
R. Hugh F. Bender ◽  
Benjamen T O'Donnell ◽  
Bhupinder Shergill ◽  
Brittany Q Pham ◽  
Damie J Juat ◽  
...  
Keyword(s):  
Immune Cell ◽  
Ex Vivo ◽  
Cell Damage ◽  
Three Dimensional ◽  
Human Islets ◽  
Culture Conditions ◽  
Β Cells ◽  
Standard Culture ◽  
Key Steps

Insulin is an essential regulator of blood glucose homeostasis that is produced exclusively by β cells within the pancreatic islets of healthy individuals. In those affected by diabetes, immune inflammation, damage, and destruction of islet β cells leads to insulin deficiency and hyperglycemia. Current efforts to understand the mechanisms underlying β cell damage in diabetes rely on in vitro-cultured cadaveric islets. However, isolation of these islets involves removal of crucial matrix and vasculature that supports islets in the intact pancreas. Unsurprisingly, these islets demonstrate reduced functionality over time in standard culture conditions, thereby limiting their value for understanding native islet biology. Leveraging a novel, vascularized micro-organ (VMO) approach, we have recapitulated elements of the native pancreas by incorporating isolated human islets within a three-dimensional matrix nourished by living, perfusable blood vessels. Importantly, these islets show long-term viability and maintain robust glucose-stimulated insulin responses. Furthermore, vessel-mediated delivery of immune cells to these tissues provides a model to assess islet-immune cell interactions and subsequent islet killing -- key steps in type 1 diabetes pathogenesis. Together, these results establish the islet-VMO as a novel, ex vivo platform for studying human islet biology in both health and disease.

scholarly journals Human Organ-Specific 3D Cancer Models Produced by the Stromal Self-Assembly Method of Tissue Engineering for the Study of Solid Tumors

2020 ◽  
Vol 2020 ◽  
pp. 1-23 ◽  
Author(s):  
Vincent Roy ◽  
Brice Magne ◽  
Maude Vaillancourt-Audet ◽  
Mathieu Blais ◽  
Stéphane Chabaud ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Tumor Microenvironment ◽  
Self Assembly ◽  
The Self ◽  
Human Organ ◽  
Assembly Method ◽  
Cancer Models ◽  
Organ Specific

Cancer research has considerably progressed with the improvement of in vitro study models, helping to understand the key role of the tumor microenvironment in cancer development and progression. Over the last few years, complex 3D human cell culture systems have gained much popularity over in vivo models, as they accurately mimic the tumor microenvironment and allow high-throughput drug screening. Of particular interest, in vitrohuman 3D tissue constructs, produced by the self-assembly method of tissue engineering, have been successfully used to model the tumor microenvironment and now represent a very promising approach to further develop diverse cancer models. In this review, we describe the importance of the tumor microenvironment and present the existing in vitro cancer models generated through the self-assembly method of tissue engineering. Lastly, we highlight the relevance of this approach to mimic various and complex tumors, including basal cell carcinoma, cutaneous neurofibroma, skin melanoma, bladder cancer, and uveal melanoma.

scholarly journals Mesenchymal-like glioma cells are enriched in the gelatin methacrylate hydrogels

2021 ◽  
Author(s):  
Nameeta Shah ◽  
Pavan M. Hallur ◽  
Raksha A. Ganesh ◽  
Pranali Sonpatki ◽  
Divya Naik ◽  
...  
Keyword(s):  
Therapeutic Response ◽  
Immune Cell ◽  
Three Dimensional ◽  
Glioma Cells ◽  
Cellular Phenotype ◽  
3D Scaffold ◽  
Promising Alternative ◽  
Cells Cultured

AbstractGlioblastoma is the most lethal primary malignant brain tumor in adults. Simplified two-dimensional (2D) cell culture and neurospheres in vitro models fail to recapitulate the complexity of the tumor microenvironment, limiting its ability to predict therapeutic response. Three-dimensional (3D) scaffold-based models have emerged as a promising alternative for addressing these concerns. One such 3D system is gelatin methacrylate (GelMA) hydrogels, which can be used for modeling the glioblastoma microenvironment. We characterized the phenotype of patient-derived glioma cells cultured in GelMA hydrogels (3D-GMH) for their tumorigenic properties using invasion and chemoresponse assays. In addition, we used integrated single-cell and spatial transcriptome analysis to compare cells cultured in 3D-GMH to cells in vivo. Finally, we assessed tumor-immune cell interactions with a macrophage infiltration assay and a cytokine array. We show that cells cultured in 3D-GMH develop a mesenchymal-like cellular phenotype found in perivascular and hypoxic regions present in the core of the tumor, and recruit macrophages by secreting cytokines in contrast to the cells grown as neurospheres that match the phenotype of cells of the infiltrative edge of the tumor.

Lignocellulose fibers elaborating super-swollen three-dimensional cellulose hydrogels from solution in N,N-dimethylacetamide/lithium chloride

TAPPI Journal ◽  
2018 ◽  
Vol 17 (02) ◽  
pp. 81-88
Author(s):  
Aleksandra Mikhailidi ◽  
Shahriar Karim Saurov ◽  
Seppo Anderson ◽  
Nina Kotelnikova
Keyword(s):  
Lithium Chloride ◽  
Self Assembly ◽  
Three Dimensional ◽  
Scattering Method ◽  
High Porosity ◽  
Gelation Mechanism ◽  
Ph Change ◽  
Surface Areas ◽  
Lignocellulose Fibers

Super-swollen hydrogels were prepared in vitro from lignocelluloses of various origins via direct dissolving in N,N-dimethylacetamide/lithium chloride (DMAc/LiCl) followed by regeneration from solutions. The hydrogels retained a large amount of water (up to 2500 wt%) and had high porosity and specific surface areas. Superabsorbance of the hydrogels was confirmed with a wide angle X-ray scattering method. The hydrogels seem to be smart matters due to PH-dependent behavior by swelling and pH change experiments. The gelation mechanism includes spontaneous self-assembly from the solutions in DMAc/LiCl, due to the reconstruction of new hydrogen bond webs between lignocellulose chains and water. The hydrogels exhibited high stability but their morphology changed while drying due to water removal and the collapse of the H-bonds.

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