Human immunity in vitro — Solving immunogenicity and more

Giese, Christoph; Marx, Uwe

doi:10.1016/j.addr.2013.12.011

Cited by 56 publications

(67 citation statements)

References 230 publications

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“…Giese and Marx 120 provide an excellent review that discusses how to emulate in vitro innate immunity in nonlymphoidal tissue and adaptive immune responses in lymphoidal tissue. At the end of their review, they succinctly assess the status of in vitro immune models:…”

Section: Mps Immunologymentioning

confidence: 99%

“…126 A central problem limiting the current procedures of testing immunotherapies is the phylogenetic distance between laboratory animals and humans, such that some pathogens can affect one species but not another, and there are significant differences in innate and adaptive immune cells between species. 120 But there are differences between people. We have already seen the inclusion of macrophages, glial cells, and Kupffer cells in MPS studies, but these cells are part of the innate immune system, which does not separate "self" from "not self."…”

Section: Mps Immunologymentioning

confidence: 99%

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Fitting tissue chips and microphysiological systems into the grand scheme of medicine, biology, pharmacology, and toxicology

Watson

Hunziker

Wikswo

2017

Exp Biol Med (Maywood)

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Impact statementMicrophysiological systems (MPS), which include engineered organoids and both individual and coupled organs-on-chips and tissue chips, are a rapidly growing topic of research that addresses the known limitations of conventional cellular monoculture on flat plastic -a wellperfected set of techniques that produces reliable, statistically significant results that may not adequately represent human biology and disease. As reviewed in this article and the others in this thematic issue, MPS research has made notable progress in the past three years in both cell sourcing and characterization. As the field matures, currently identified challenges are being addressed, and new ones are being recognized. Building upon investments by the Defense Advanced Research Projects Agency, National Institutes of Health, Food and Drug Administration, Defense Threat Reduction Agency, and Environmental Protection Agency of more than $200 million since 2012 and sizable corporate spending, academic and commercial players in the MPS community are demonstrating their ability to meet the translational challenges required to apply MPS technologies to accelerate drug development and advance toxicology. AbstractMicrophysiological systems (MPS), which include engineered organoids (EOs), single organ/tissue chips (TCs), and multiple organs interconnected to create miniature in vitro models of human physiological systems, are rapidly becoming effective tools for drug development and the mechanistic understanding of tissue physiology and pathophysiology. The second MPS thematic issue of Experimental Biology and Medicine comprises 15 articles by scientists and engineers from the National Institutes of Health, the IQ Consortium, the Food and Drug Administration, and Environmental Protection Agency, an MPS company, and academia. Topics include the progress, challenges, and future of organs-on-chips, dissemination of TCs into Pharma, children's health protection, liver zonation, liver chips and their coupling to interconnected systems, gastrointestinal MPS, maturation of immature cardiomyocytes in a heart-on-a-chip, coculture of multiple cell types in a human skin construct, use of synthetic hydrogels to create EOs that form neural tissue models, the blood-brain barrier-on-a-chip, MPS models of coupled female reproductive organs, coupling MPS devices to create a body-on-a-chip, and the use of a microformulator to recapitulate endocrine circadian rhythms. While MPS hardware has been relatively stable since the last MPS thematic issue, there have been significant advances in cell sourcing, with increased reliance on human-induced pluripotent stem cells, and in characterization of the genetic and functional cell state in MPS bioreactors. There is growing appreciation of the need to minimize perfusate-to-cell-volume ratios and respect physiological scaling of coupled TCs. Questions asked by drug developers are followed by an analysis of the potential value, costs, and needs of Pharma. Of highest value and lowest switching costs may be the d...

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Section: Mps Immunologymentioning

confidence: 99%

Section: Mps Immunologymentioning

confidence: 99%

Fitting tissue chips and microphysiological systems into the grand scheme of medicine, biology, pharmacology, and toxicology

Watson

Hunziker

Wikswo

2017

Exp Biol Med (Maywood)

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“…In this context, many studies have focused on generating organ-on-a-chip models of the liver and kidney due to the importance of theses organs in drug metabolism and clearance [13][14][15]. Models of other important organs, e.g., lung [16,17], skin [18][19][20], and the gastrointestinal (GI) tract [21,22], have also been developed for toxicity testing, since those organs are closely related to allergic and immunogenic disorders caused by exogenous substances [23,24].…”

Section: Organ-on-a-chip: Towards Improved Toxicity Assessmentmentioning

confidence: 99%

“…In the human immune system, bone marrow adaptive immunity functions such as antibody secretion in plasma cells and maintenance of the B-and T-cell vaccination memory result from re-infection by known pathogens. T and B memory lymphocytes and plasma cells in the red marrow are distributed to non-lymphoid organs (e.g., gut, lung, skin, and liver) through the bloodstream [23]. Thus, the immunity function of non-lymphoid organs should be considered together with bone-marrow immunity when the bone-marrow-on-a-chip device is established for systemic immune mechanisms.…”

Section: Future Aspects Of Clinical/pharmaceutical Applicationsmentioning

confidence: 99%

Organ-On-A-Chip: Development and Clinical Prospects Toward Toxicity Assessment with an Emphasis on Bone Marrow

et al. 2015

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Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

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“…Recent technological advances in 2D and 3D culturing of human cells have led to major breakthroughs in the field of in vitro disease modeling. These systems range from basic immunogenicity testing via ex vivo culture of PBMCs to 3D human artificial lymph node (HuALN) bioreactors (reviewed in [4] such diverse targets as HBV, tetanus toxoid, monoclonal antibodies and YF-VAX [5][6][7]. In this study, we have extended those findings to include the differential immune responses of adult versus elderly donors to vaccination against seasonal influenza.…”

Section: Introductionmentioning

confidence: 96%

The in vitro MIMIC® platform reflects age-associated changes in immunological responses after influenza vaccination

Dauner

Agrawal

Salvatico

et al. 2017

Vaccine

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Human immunity in vitro — Solving immunogenicity and more

Cited by 56 publications

References 230 publications

Fitting tissue chips and microphysiological systems into the grand scheme of medicine, biology, pharmacology, and toxicology

Fitting tissue chips and microphysiological systems into the grand scheme of medicine, biology, pharmacology, and toxicology

Organ-On-A-Chip: Development and Clinical Prospects Toward Toxicity Assessment with an Emphasis on Bone Marrow

The in vitro MIMIC® platform reflects age-associated changes in immunological responses after influenza vaccination

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