Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems

Trevisan, Marta; Sinigaglia, Alessandro; Desole, Giovanna; Berto, Alessandro; Pacenti, Monia; Palù, Giorgio; Barzon, Luisa

doi:10.3390/v7072800

Cited by 27 publications

(21 citation statements)

References 113 publications

(129 reference statements)

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“…For instance, recent biotechnology breakthrough of iPSC technology can be included in developing patient-specific neural, liver, cardiac, and brain tissue models with viral or bacterial infections. The patientspecific iPSC-derived in vitro disease models will provide a versatile and non-invasive platform, which allow for the investigation of patientpathogen interactions and the discovery of personalized medicine [272]. Conversely, by exposing patient-derived viruses (such as HBV) or bacteria to an established in vitro model, it provides us an opportunity to analyze the patient-specific immune responses towards the infection and thus enables the understanding and discovering of the immune evasion pathways and biomarkers [209].…”

Section: Summary and Future Outlookmentioning

confidence: 99%

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

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A B S T R A C TBacterial infections and antibiotic resistant bacteria have become a growing problem over the past decade. As a result, the Centers for Disease Control predict more deaths resulting from microorganisms than all cancers combined by 2050. Currently, many traditional models used to study bacterial infections fail to precisely replicate the in vivo bacterial environment. These models often fail to incorporate fluid flow, bio-mechanical cues, intercellular interactions, host-bacteria interactions, and even the simple inclusion of relevant physiological proteins in culture media. As a result of these inadequate models, there is often a poor correlation between in vitro and in vivo assays, limiting therapeutic potential. Thus, the urgency to establish in vitro and ex vivo systems to investigate the mechanisms underlying bacterial infections and to discover new-age therapeutics against bacterial infections is dire. In this review, we present an update of current in vitro and ex vivo models that are comprehensively changing the landscape of traditional microbiology assays. Further, we provide a comparative analysis of previous research on various established organ-disease models. Lastly, we provide insight on future techniques that may more accurately test new formulations to meet the growing demand of antibiotic resistant bacterial infections. Lack of adequate model systemsCommonly, a variety of inconsistent, in vitro and in vivo models have been progressively utilized for antibiotic/drug development and pathophysiological studies. These systems range from simple in vitro models using microtiter plate assays and flow cells to more complex in https://doi.

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Section: Summary and Future Outlookmentioning

confidence: 99%

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

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“…Stem cell derived hepatocytes have also become invaluable for use in modelling infectious diseases such as hepatitis C virus (HCV) infection [93][94][95] and malaria in order to establish effective systems to investigate disease progression and assays for drug screening. Various groups [33,96] employed the use of hiPSC-HEPs in investigating HCV infection.…”

Section: Applications Of Hipsc-hepsmentioning

confidence: 99%

The potential of induced pluripotent stem cell derived hepatocytes

Hannoun

Steichen

Dianat

et al. 2016

Journal of Hepatology

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Orthotopic liver transplantation remains the only curative treatment for liver disease. However, the number of patients who die while on the waiting list (15%) has increased in recent years as a result of severe organ shortages; furthermore the incidence of liver disease is increasing worldwide. Clinical trials involving hepatocyte transplantation have provided encouraging results. However, transplanted cell function appears to often decline after several months, necessitating liver transplantation. The precise aetiology of the loss of cell function is not clear, but poor engraftment and immune-mediated loss appear to be important factors. Also, primary human hepatocytes (PHH) are not readily available, de-differentiate, and die rapidly in culture. Hepatocytes are available from other sources, such as tumour-derived human hepatocyte cell lines and immortalised human hepatocyte cell lines or porcine hepatocytes. However, all these cells suffer from various limitations such as reduced or differences in functions or risk of zoonotic infections. Due to their significant potential, one possible inexhaustible source of hepatocytes is through the directed differentiation of human induced pluripotent stem cells (hiPSCs). This review will discuss the potential applications and existing limitations of hiPSC-derived hepatocytes in regenerative medicine, drug screening, in vitro disease modelling and bioartificial livers.

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“…Disease modeling using iPSCs is not restricted to diseases with genetic causes, in fact, patient-specific iPSC-derived cells can be utilized as platforms to analyze host–pathogen interactions, where the cells are infected with a virus and studied. iPSC-derived cells are more accurate representatives of human physiology as compared to animal models [ 129 ]. iPSC-based disease modeling is particularly useful for studying viruses that are highly species-specific, or that can only grow in a restricted number of cell types, specifically those that may be hard to isolate and culture [ 129 ].…”

Section: Examples Of Disease Modelsmentioning

confidence: 99%

“…iPSC-derived cells are more accurate representatives of human physiology as compared to animal models [ 129 ]. iPSC-based disease modeling is particularly useful for studying viruses that are highly species-specific, or that can only grow in a restricted number of cell types, specifically those that may be hard to isolate and culture [ 129 ]. For example, herpes simplex virus (HSV) and varicella zoster virus (VZV) have tropism for neural cells and establish latency in sensory neurons, and these cell types can be generated from iPSCs to enable further study of these viruses.…”

Section: Examples Of Disease Modelsmentioning

confidence: 99%

Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges

Seah

Farran

Warrier

et al. 2015

IJMS

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Embryonic stem cells (ESCs) are chiefly characterized by their ability to self-renew and to differentiate into any cell type derived from the three main germ layers. It was demonstrated that somatic cells could be reprogrammed to form induced pluripotent stem cells (iPSCs) via various strategies. Gene editing is a technique that can be used to make targeted changes in the genome, and the efficiency of this process has been significantly enhanced by recent advancements. The use of engineered endonucleases, such as homing endonucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and Cas9 of the CRISPR system, has significantly enhanced the efficiency of gene editing. The combination of somatic cell reprogramming with gene editing enables us to model human diseases in vitro, in a manner considered superior to animal disease models. In this review, we discuss the various strategies of reprogramming and gene targeting with an emphasis on the current advancements and challenges of using these techniques to model human diseases.

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Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems

Cited by 27 publications

References 113 publications

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

The potential of induced pluripotent stem cell derived hepatocytes

Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges

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