A dynamic microscale mid-throughput fibrosis model to investigate the effects of different ratios of cardiomyocytes and fibroblasts

Mainardi, Andrea; Carminati, Francesca; Ugolini, Giovanni Stefano; Occhetta, Paola; Isu, Giuseppe; Diaz, Diana Robles; Reid, Gregory; Visone, Roberta; Rasponi, Marco; Marsano, Anna

doi:10.1039/d1lc00092f

Cited by 17 publications

(11 citation statements)

References 47 publications

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“…The same principle was recently incorporated in a multichamber mechanically active OoC device with an increased throughput (Mainardi et al, 2021). The device (Figure 4A) is composed of a top cell culture chamber and a compression chamber divided by a thin PDMS membrane.…”

Section: Ooc Systems With Mechanical Loading Regimes Suitable For Ivd Researchmentioning

confidence: 99%

Intervertebral Disc-on-a-Chip as Advanced In Vitro Model for Mechanobiology Research and Drug Testing: A Review and Perspective

Mainardi

Cambria

Occhetta

et al. 2022

Front. Bioeng. Biotechnol.

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Discogenic back pain is one of the most diffused musculoskeletal pathologies and a hurdle to a good quality of life for millions of people. Existing therapeutic options are exclusively directed at reducing symptoms, not at targeting the underlying, still poorly understood, degenerative processes. Common intervertebral disc (IVD) disease models still do not fully replicate the course of degenerative IVD disease. Advanced disease models that incorporate mechanical loading are needed to investigate pathological causes and processes, as well as to identify therapeutic targets. Organs-on-chip (OoC) are microfluidic-based devices that aim at recapitulating tissue functions in vitro by introducing key features of the tissue microenvironment (e.g., 3D architecture, soluble signals and mechanical conditioning). In this review we analyze and depict existing OoC platforms used to investigate pathological alterations of IVD cells/tissues and discuss their benefits and limitations. Starting from the consideration that mechanobiology plays a pivotal role in both IVD homeostasis and degeneration, we then focus on OoC settings enabling to recapitulate physiological or aberrant mechanical loading, in conjunction with other relevant features (such as inflammation). Finally, we propose our view on design criteria for IVD-on-a-chip systems, offering a future perspective to model IVD mechanobiology.

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Section: Ooc Systems With Mechanical Loading Regimes Suitable For Ivd Researchmentioning

confidence: 99%

Intervertebral Disc-on-a-Chip as Advanced In Vitro Model for Mechanobiology Research and Drug Testing: A Review and Perspective

Mainardi

Cambria

Occhetta

et al. 2022

Front. Bioeng. Biotechnol.

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“…46 Inclusion of CFs in human HOCs has become a paradigm in many HOC models. [48][49][50] Therefore, to develop accurate HOC models of cardiac fibrosis, researchers have often targeted the CF through the administration of exogenous growth factors/cytokines, via induction of pathological mechanical forces, or by altering the ratio of CMs to CFs within the HOC devices. Notably, CFs cultured on hard plastic in 2D take on an activated, pro-fibrotic phenotype characterized by upregulation of αSMA (alpha-smooth muscle actin).…”

Section: Fibrosismentioning

confidence: 99%

Modeling Heart Diseases on a Chip: Advantages and Future Opportunities

Mourad

Yee

et al. 2023

Circulation Research

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Heart disease is a significant burden on global health care systems and is a leading cause of death each year. To improve our understanding of heart disease, high quality disease models are needed. These will facilitate the discovery and development of new treatments for heart disease. Traditionally, researchers have relied on 2D monolayer systems or animal models of heart disease to elucidate pathophysiology and drug responses. Heart-on-a-chip (HOC) technology is an emerging field where cardiomyocytes among other cell types in the heart can be used to generate functional, beating cardiac microtissues that recapitulate many features of the human heart. HOC models are showing great promise as disease modeling platforms and are poised to serve as important tools in the drug development pipeline. By leveraging advances in human pluripotent stem cell-derived cardiomyocyte biology and microfabrication technology, diseased HOCs are highly tuneable and can be generated via different approaches such as: using cells with defined genetic backgrounds (patient-derived cells), adding small molecules, modifying the cells’ environment, altering cell ratio/composition of microtissues, among others. HOCs have been used to faithfully model aspects of arrhythmia, fibrosis, infection, cardiomyopathies, and ischemia, to name a few. In this review, we highlight recent advances in disease modeling using HOC systems, describing instances where these models outperformed other models in terms of reproducing disease phenotypes and/or led to drug development.

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“…In the first case, cardiomyocytes from human induced pluripotent stem cells and human fibroblasts are embedded in a fibrin hydrogel and cultured within uHeart by using a heartbeat-like mechanical training to develop synchronously beating cardiac microtissues, as confirmed by on-chip electrophysiology studies. 51 Cardiac pathological models have also been developed by tuning mechanical environments, demonstrating the versatility of uHeart in modelling cardiac fibrosis (uScar) 52,53 and inherited cardiomyopathies, among others. uKnee provides 3-D cartilage-on-a-chip with hyperphysiological (HP) compression (30%, 1 Hz), sufficient to elicit osteoarthritis (OA) pathogenesis in vitro.…”

Section: Industrial Adoption Of Integrated Micro Physiological System...mentioning

confidence: 99%

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022

Naik,

Vadloori,

Poosala

et al. 2023

Altern Lab Anim

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Animal experimentation has been integral to drug discovery and development and safety assessment for many years, since it provides insights into the mechanisms of drug efficacy and toxicity (e.g. pharmacology, pharmacokinetics and pharmacodynamics). However, due to species differences in physiology, metabolism and sensitivity to drugs, the animal models can often fail to replicate the effects of drugs and chemicals in human patients, workers and consumers. Researchers across the globe are increasingly applying the Three Rs principles by employing innovative methods in research and testing. The Three Rs concept focuses on: the replacement of animal models (e.g. with in vitro and in silico models or human studies), on the reduction of the number of animals required to achieve research objectives, and on the refinement of existing experimental practices (e.g. eliminating distress and enhancing animal wellbeing). For the last two years, Oncoseek Bio-Acasta Health, a 3-D cell culture-based cutting-edge translational biotechnology company, has organised an annual International Conference on 3Rs Research and Progress. This series of global conferences aims to bring together researchers with diverse expertise and interests, and provides a platform where they can share and discuss their research to promote practices according to the Three Rs principles. In November 2022, the 3rd international conference, Advances in Animal Models and Cutting-Edge Research in Alternatives, took place at the GITAM University in Vishakhapatnam (AP, India) in a hybrid format (i.e. online and in-person). These conference proceedings provide details of the presentations, which were categorised under five different topic sessions. It also describes a special interactive session on in silico strategies for preclinical research in oncology, which was held at the end of the first day.

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A dynamic microscale mid-throughput fibrosis model to investigate the effects of different ratios of cardiomyocytes and fibroblasts

Abstract: High percentages of cardiomyocytes mitigate the onset of fibrotic traits induced by fibroblasts in a mid-throughput, mechanically active microdevice.

Cited by 17 publications

References 47 publications

Intervertebral Disc-on-a-Chip as Advanced In Vitro Model for Mechanobiology Research and Drug Testing: A Review and Perspective

Intervertebral Disc-on-a-Chip as Advanced In Vitro Model for Mechanobiology Research and Drug Testing: A Review and Perspective

Modeling Heart Diseases on a Chip: Advantages and Future Opportunities

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022

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