Human‐on‐a‐Chip Systems: Long‐Term Electrical and Mechanical Function Monitoring of a Human‐on‐a‐Chip System (Adv. Funct. Mater. 8/2019)

Oleaga, Carlota; Lavado, Andrea; Riu, Anne; Rothemund, Sandra; Carmona‐Moran, Carlos A.; Persaud, Keisha; Yurko, Andrew; Lear, Jennifer; Narasimhan, Narasimhan Sriram; Long, Christopher J.; Sommerhage, Frank; Bridges, Lee; Cai, Yuanqing; Martin, Candace; Schnepper, Mark T.; Goswami, Arindom; Note, Reine; Langer, Jessica; Teissier, Silvia; Cotovio, José; Hickman, James J.

doi:10.1002/adfm.201970049

Cited by 30 publications

(8 citation statements)

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“…[15] In our lab, these systems have demonstrated the ability to predict known toxicity profiles for established drugs such as terfenadine and cyclophosphamide [16] and tamoxifen [17] indicating their potential for preclinical evaluation of novel compounds to treat disease. [18] Additionally, we have shown multi-organ HoaC systems can maintain organ physiology for up to 28 days in serum-free medium [19] as well as reproduce the basic responses of the innate immune system. [20] In the context of rare diseases, bioengineered HoaC systems hold promise for modeling complex pathophysiology, uncovering disease mechanisms, and determining the therapeutic efficacy and safety of novel compounds using clinically relevant assays, especially for biopharmaceuticals.…”

Section: Introductionmentioning

confidence: 91%

Classical Complement Pathway Inhibition in a “Human‐On‐A‐Chip” Model of Autoimmune Demyelinating Neuropathies

Rumsey

Lorance

Jackson

et al. 2022

Advanced Therapeutics

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Chronic autoimmune demyelinating neuropathies are a group of rare neuromuscular disorders with complex, poorly characterized etiology. Here the authors describe a phenotypic, human-on-a-chip (HoaC) electrical conduction model of two rare autoimmune demyelinating neuropathies, chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN), and explore the efficacy of TNT005, a monoclonal antibody inhibitor of the classical complement pathway. Patient sera is shown to contain anti-GM1 IgM and IgG antibodies capable of binding to human primary Schwann cells and induced pluripotent stem cell-derived motoneurons (MNs). Patient autoantibody binding is sufficient to activate the classical complement pathway, resulting in detection of C3b and C5b-9. A HoaC model, using a microelectrode array with directed axonal outgrowth over the electrodes treated with patient sera, exhibits reductions in MN action potential frequency and conduction velocity. TNT005 rescued the serum-induced complement deposition and functional deficits while treatment with an isotype control antibody has no rescue effect. These data indicate that complement activation by CIDP and MMN patient serum is sufficient to mimic neurophysiological features of each disease and that complement inhibition with TNT005 is sufficient to rescue these pathological effects and provide efficacy data included in an investigational new drug application, demonstrating the model's translational potential.

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Section: Introductionmentioning

confidence: 91%

Classical Complement Pathway Inhibition in a “Human‐On‐A‐Chip” Model of Autoimmune Demyelinating Neuropathies

Rumsey

Lorance

Jackson

et al. 2022

Advanced Therapeutics

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“…The minimum interval for animal trials to assess repeat dosage toxicity is four weeks, consistent with their proposed platform in terms of preserving the viability of cells (Figure 11b). [179] An interesting MOC study, albeit without integrated sensing, is from Skardal et al; they proposed a group of bioengineered tissue constructs and tissue organoids incorporated in a closed circulatory perfusion system, enabling inter-organ communication. They proposed a three-tissue OoC system, including heart, liver, and lung, and studied how drug administration affects the organs′ interactions.…”

Section: Advanced Microphysiological Systems For Multiorgan-on-a-chip...mentioning

confidence: 99%

“…b-ii) 2D illustration of the platform along with different sensing parameters for each organ. Reproduced with permission [179]. Copyright 2019, John Wiley & Sons, Inc. c) The graphical illustration of the MOC platform presented by Herland et al which connects three organs on a chip device including gut, liver, and kidney in which the mentioned chips are fluidically connected.…”

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confidence: 99%

Advanced Materials and Sensors for Microphysiological Systems: Focus on Electronic and Electrooptical Interfaces

2022

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Advanced in vitro cell culture systems or microphysiological systems (MPSs), including microfluidic organ‐on‐a‐chip (OoC), are breakthrough technologies in biomedicine. These systems recapitulate features of human tissues outside of the body. They are increasingly being used to study the functionality of different organs for applications such as drug evolutions, disease modeling, and precision medicine. Currently, developers and endpoint users of these in vitro models promote how they can replace animal models or even be a better ethically neutral and humanized alternative to study pathology, physiology, and pharmacology. Although reported models show a remarkable physiological structure and function compared to the conventional 2D cell culture, they are almost exclusively based on standard passive polymers or glass with none or minimal real‐time stimuli and readout capacity. The next technology leap in reproducing in vivo‐like functionality and real‐time monitoring of tissue function could be realized with advanced functional materials and devices. This review describes the currently reported electronic and optical advanced materials for sensing and stimulation of MPS models. In addition, an overview of multi‐sensing for Body‐on‐Chip platforms is given. Finally, one gives the perspective on how advanced functional materials could be integrated into in vitro systems to precisely mimic human physiology.

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“…Impedance-based techniques can be further enhanced when coupled with multi-electrode arrays to provide localized sensing and electrical stimulation in relevant microenvironments of an organismoid. Applications include the recapitulation of cardiomyocyte or motor neuron innervation by direct electrical stimulation of the contractile activity (153), and the possibility of producing surrogate electroencephalograms from neuronal activities, which represents an added value to Parkinson or Alzheimer's disease modeling.…”

Section: Microfluidic Cell Culture Systems-the Key Toward the Integration Of Premature Organoids Into Organismoidsmentioning

confidence: 99%

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

Marx

Accastelli²,

David

et al. 2021

Front. Med.

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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.

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Human‐on‐a‐Chip Systems: Long‐Term Electrical and Mechanical Function Monitoring of a Human‐on‐a‐Chip System (Adv. Funct. Mater. 8/2019)

Cited by 30 publications

References 0 publications

Classical Complement Pathway Inhibition in a “Human‐On‐A‐Chip” Model of Autoimmune Demyelinating Neuropathies

Classical Complement Pathway Inhibition in a “Human‐On‐A‐Chip” Model of Autoimmune Demyelinating Neuropathies

Advanced Materials and Sensors for Microphysiological Systems: Focus on Electronic and Electrooptical Interfaces

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

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