4.7 Review

Microphysiological systems meet hiPSC technology - New tools for disease modeling of liver infections in basic research and drug development

Journal

ADVANCED DRUG DELIVERY REVIEWS
Volume 140, Issue -, Pages 51-67

Publisher

ELSEVIER
DOI: 10.1016/j.addr.2018.06.008

Keywords

Hepatocyte like cells (HLC); Viral liver infections; Malaria; Inflammation; Stem cells; iPSC differentiation; Immune response; Drug screening

Funding

  1. Federal Ministry of Education and Research [01EK1612B, 01EO1002]
  2. German Research Foundation [MO 2968/1-1, SFB 1278]
  3. German Federal Institute for Risk Assessment [1328-511]
  4. German Research Platform for Zoonoses [01KI1109]
  5. Federal Construction Bank Thiwingia [2011 VF 0005]
  6. Center for Sepsis Control and Care, Jena [G4.3]

Ask authors/readers for more resources

Complex cell culture models such as microphysiological models (MPS) mimicking human liver functionality in vitro are in the spotlight as alternative to conventional cell culture and animal models. Promising techniques like microfluidic cell culture or micropatterning by 3D bioprinting are gaining increasing importance for the development of MPS to address the needs for more predictivity and cost efficiency. In this context, human induced pluripotent stem cells (hiPSCs) offer new perspectives for the development of advanced liver-on-chip systems by recreating an in vivo like microenvironment that supports the reliable differentiation of hiPSCs to hepatocyte-like cells (HLC). In this review we will summarize current protocols of HLC generation and highlight recently established MPS suitable to resemble physiological hepatocyte function in vitro. In addition, we are discussing potential applications of liver MPS for disease modeling related to systemic or direct liver infections and the use of MPS in testing of new drug candidates. (C) 2018 The Authors. Published by Elsevier B.V.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Anesthesiology

Coronavirus disease 2019 (COVID-19): update for anesthesiologists and intensivists March 2020

D. Thomas-Rueddel, J. Winning, P. Dickmann, D. Ouart, A. Kortgen, U. Janssens, M. Bauer

Summary: The current outbreak of COVID-19 in Germany has both mild cases and severe cases that require intensive care. Unlike other infectious diseases, severe cases of COVID-19 show a prolonged progression from first symptoms to life-threatening deterioration of lung function. It is crucial to prevent nosocomial infections and maintain hospitals' operational capability, with departments of Anaesthesia, Intensive Care, and emergency medicine facing major challenges.

ANAESTHESIST (2021)

Article Biochemical Research Methods

In vivo coherent anti-Stokes Raman scattering microscopy reveals vitamin A distribution in the liver

Marko Rodewald, Hyeonsoo Bae, Sophie Huschke, Tobias Meyer-Zedler, Michael Schmitt, Adrian Tibor Press, Stephanie Schubert, Michael Bauer, Juergen Popp

Summary: The microscope setup presented in this study is tailored to address challenges in in vivo experiments, showcasing its use in identifying vitamin A accumulations in the liver and marking the positions of hepatic stellate cells. These cells, being the main source of extracellular matrix protein after hepatic injury, are key targets for novel nanomedical strategies in liver fibrosis treatment and their role in vitamin A metabolism makes them ideal for a CARS-based approach.

JOURNAL OF BIOPHOTONICS (2021)

Article Dermatology

3D-SeboSkin Model for Human ex vivo Studies of Hidradenitis Suppurativa/Acne Inversa

Xiaoxiao Hou, Amir M. Hossini, Georgios Nikolakis, Ottfried Balthasar, Andreas Kurtz, Christos C. Zouboulis

Summary: This study developed a human model of hidradenitis suppurativa/acne inversa (HS) applicable for preclinical research to understand the pathophysiology of the disease and determine the action of therapeutic candidates. The application of 3D-SeboSkin technology maintained the structural integrity of lesional and perilesional HS skin ex vivo, preserving the differential expression and pattern of several HS biomarkers. The HS 3D-SeboSkin model was validated as a reproducible, human model suitable for preclinical studies of HS skin lesions and perilesional areas.

DERMATOLOGY (2022)

Letter Oncology

The impact of specific cytokine directed treatment on severe COVID-19

P. A. Reuken, M. M. Ruethrich, A. Hochhaus, J. Hammersen, M. Bauer, P. La Rosee, F. La Rosee, A. Stallmach

LEUKEMIA (2021)

Article Multidisciplinary Sciences

The role of risk communication in public health interventions. An analysis of risk communication for a community quarantine in Germany to curb the SARS-CoV-2 pandemic

Juliane Scholz, Wibke Wetzker, Annika Licht, Rainer Heintzmann, Andre Scherag, Sebastian Weis, Mathias Pletz, Cornelia Betsch, Michael Bauer, Petra Dickmann

Summary: The investigation of a community quarantine in Neustadt am Rennsteig, Germany, revealed that national television was the most important information channel, while contact with local authorities was limited. Most participants supported the quarantine measures and reported high compliance. Participants with higher levels of concern and information were more likely to accept and comply with quarantine measures.

PLOS ONE (2021)

Article Cell Biology

Functional differentiation and scalable production of renal proximal tubular epithelial cells from human pluripotent stem cells in a dynamic culture system

Thao Thi Thanh Ngo, Bella Rossbach, Isabelle Sebastien, Julia C. Neubauer, Andreas Kurtz, Krithika Hariharan

Summary: This study provides a standardized protocol for the large-scale production of proximal tubular epithelial cells (PTEC) generated from human pluripotent stem cells (hPSC). The researchers successfully expanded and differentiated hPSC into PTEC using a bioLevitator platform and matrix-coated alginate beads. The functional PTEC exhibited microvilli and clear apico-basal localization of markers, and showed active reabsorption and response to drug treatment. This method may have the potential for automatable production of functional human PTEC.

CELL PROLIFERATION (2022)

Article Engineering, Biomedical

Invasive aspergillosis-on-chip: A quantitative treatment study of human Aspergillus fumigatus infection

T. N. M. Hoang, Z. Cseresnyes, S. Hartung, M. Blickensdorf, C. Saffer, K. Rennert, A. S. Mosig, M. von Lilienfeld-Toal, M. T. Figge

Summary: Invasive pulmonary aspergillosis is a serious infection with a high mortality rate. The invasive aspergillosis-on-chip (IAC) model allows the study of fungal growth and invasion in vitro. The model uses an algorithm-based analysis pipeline to visualize and quantify the morphology of the fungus. Macrophages in the IAC model inhibit fungal growth partially and contribute to the release of proinflammatory cytokines and chemokines. The fungistatic drug caspofungin limits fungal growth and causes morphological changes in the hyphal tree.

BIOMATERIALS (2022)

Review Cell Biology

Human pluripotent stem cell registry: Operations, role and current directions

Andreas Kurtz, Nancy Mah, Ying Chen, Antonie Fuhr, Sabine Kobold, Stefanie Seltmann, Sabine C. Mueller

Summary: This review provides an overview of the establishment and mission of the human pluripotent stem cell registry (hPSCreg), as well as its development into a knowledgebase for hPSC and the current status of hPSC-focused databases. It also discusses the challenges and hurdles of data sharing on a global level.

CELL PROLIFERATION (2022)

Article Cell & Tissue Engineering

Transposon-mediated glial cell line-derived neurotrophic factor overexpression in human adipose tissue-derived mesenchymal stromal cells: A potential approach for neuroregenerative medicine?

Justyna Rasinska, Charlotte Klein, Laura Stahn, Felix Maidhof, Anna Pfeffer, Stefanie Schreyer, Manfred Gossen, Andreas Kurtz, Barbara Steiner, Shabnam Hemmati-Sadeghi

Summary: This study achieved continuous overexpression of GDNF in immune-privileged human adipose tissue-derived mesenchymal stromal cells using a non-viral Sleeping Beauty transposon. Although GDNF was detectable shortly after cell transplantation, the 6-OHDA model used was too mild to evaluate disease improvement. Further research using a more appropriate 6-OHDA model is needed to test the therapeutic potential of GDNF-overexpressing cells.

JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE (2022)

Review Biochemistry & Molecular Biology

Studying metabolism with multi-organ chips: new tools for disease modelling, pharmacokinetics and pharmacodynamics

Tanvi Shroff, Kehinde Aina, Christian Maass, Madalena Cipriano, Joeri Lambrecht, Frank Tacke, Alexander Mosig, Peter Loskill

Summary: Non-clinical models for studying metabolism have limitations in terms of species translatability and predictability. Organ-on-chip systems, specifically multi-organ chips, provide a species-specific platform for studying metabolism and can be integrated with in silico models to enhance predictive power. This technology also has potential for translational applications and personalized medicine.

OPEN BIOLOGY (2022)

Article Cell Biology

Human iPSC-Derived Renal Cells Change Their Immunogenic Properties during Maturation: Implications for Regenerative Therapies

Bella Rossbach, Krithika Hariharan, Nancy Mah, Su-Jun Oh, Hans-Dieter Volk, Petra Reinke, Andreas Kurtz

Summary: This study investigates the immunological effects of hiPSC-derived cells and finds that their immune response varies depending on the stage of cell maturation. Autologous and allogeneic T cells tolerate early renal progenitors and mature renal epithelial cells, while NK cell responses are not suppressed and can effectively change NK cell activation status. These findings have important implications for the success of cell therapies.

CELLS (2022)

Letter Critical Care Medicine

Response to the Correspondence of Helbing et al. Mouse sepsis models: don't forget ambient temperature!

Michael Bauer, Reinhard Wetzker

INTENSIVE CARE MEDICINE EXPERIMENTAL (2022)

Article Biochemistry & Molecular Biology

Redefining critical illness

David M. Maslove, Benjamin Tang, Manu Shankar-Hari, Patrick R. Lawler, Derek C. Angus, J. Kenneth Baillie, Rebecca M. Baron, Michael Bauer, Timothy G. Buchman, Carolyn S. Calfee, Claudia C. dos Santos, Evangelos J. Giamarellos-Bourboulis, Anthony C. Gordon, John A. Kellum, Julian C. Knight, Aleksandra Leligdowicz, Daniel F. McAuley, Anthony S. McLean, David K. Menon, Nuala J. Meyer, Lyle L. Moldawer, Kiran Reddy, John P. Reilly, James A. Russell, Jonathan E. Sevransky, Christopher W. Seymour, Nathan I. Shapiro, Mervyn Singer, Charlotte Summers, Timothy E. Sweeney, B. Taylor Thompson, Tom van der Poll, Balasubramanian Venkatesh, Keith R. Walley, Timothy S. Walsh, Lorraine B. Ware, Hector R. Wong, Zsolt E. Zador, John C. Marshall

Summary: The authors propose a new conceptual model of critical illness that moves away from the current syndrome-based framework and focuses on more precise biological descriptors. They discuss the need to reconsider the current approach based on syndromes and instead emphasize the underlying biological changes that underpin critical illness states. By doing so, they believe it will lead to a better understanding of the pathobiology of critical illness and improved patient outcomes.

NATURE MEDICINE (2022)

Review Biochemistry & Molecular Biology

Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections

Lisa-Marie Ney, Maximilian Wipplinger, Martha Grossmann, Nicole Engert, Valentin D. Wegner, Alexander S. Mosig

Summary: The human intestinal microbiome has a significant impact on human health and resistance to infections through the dynamic composition and release of microbial-derived metabolites. Short-chain fatty acids (SCFA), which are produced by commensal bacteria through fermentation of indigestible fibers, play a key role in regulating the host immune response to microbial colonization by influencing various cellular processes. While the pleiotropic functions of SCFAs and their importance in maintaining human health have been studied, there is still a need for a better understanding of their mechanisms of action across different cell types and organs. This review provides an overview of the functions of SCFAs in cellular metabolism, with a focus on their role in orchestrating the immune response along different axes. It also discusses their potential use in treating inflammatory diseases and infections, as well as the use of human three-dimensional organ models for further research.

OPEN BIOLOGY (2023)

Article Cell Biology

Host extracellular vesicles confer cytosolic access to systemic LPS licensing non-canonical inflammasome sensing and pyroptosis

Puja Kumari, Swathy O. Vasudevan, Ashley J. Russo, Skylar S. Wright, Victor Fraile-Agreda, Dylan Krajewski, Evan R. Jellison, Ignacio Rubio, Michael Bauer, Atsushi Shimoyama, Koichi Fukase, Yuanpeng Zhang, Joel S. Pachter, Sivapriya Kailasan Vanaja, Vijay A. Rathinam

Summary: This study demonstrates that extracellular vesicles can capture systemic bacterial lipopolysaccharide (LPS) and transfer it to the cytosol, triggering inflammatory responses and cell death.

NATURE CELL BIOLOGY (2023)

No Data Available