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Johns Hopkins Bloomberg School of Public HealthCAAT
 

CAAT Grants Program

Research Grants 2021-2022

Summary

  • Heinrich Sauer, Stem Cell Unit, Institute of Physiology, Justus Liebig University Gießen
    Human induced pluripotent stem cell-derived tissues to model infection, inflammation and sepsis

Abstract

Infection with viruses (including Covid-19) and bacteria induces inflammation and sepsis with frequently fatal outcome for the patient. Currently infection, inflammation and sepsis research is mainly performed in animals (mice, rats, rabbits and swine), although the inflammatory response towards infection is different between humans and animals. Infectious particles elicit a cellular immune response associated to massive global cytokine release (the cytokine storm) which is individually different between human patients and determines the severity of disease and outcome.

In the present study we undertake to generate immune-competent, vascularized tissues from human, patient-derived stem cells (iPS cells). We name this model IPSIS tissue, standing for (I)nduced (P)luripotent (S)tem cell, (I)nfection and (S)epsis. The IPSIS tissue is capable to respond towards viral and bacterial infection with an inflammatory and cellular immune response, including the cytokine storm, activation of the inflammasome, induction of oxidative stress as well as differentiation, proliferation and invasion of immuno-competent cells. 

The IPSIS tissue model can replace a variety of animal infection models.  A selection of replacable animal models currently used in infection, inflammation and sepsis research are mentioned below:
i) Mouse bacterial/viral infection model
ii) Caecal ligation and puncture (CLP) model of sepsis
iii) Toxaemia model 
iv) Colon ascendens stent peritonitis (CASP) model 

By use of the IPSIS tissue model we can recapitulate the onset and progress of infectious and inflammatory diseases in a human setting in vitro, and estimate the patient-specific response towards individualized therapies in vitro.