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Technological advancements for the development of stem cell-based models for hepatotoxicity testing

(2019) ARCHIVES OF TOXICOLOGY. 93(7). p.1789-1805
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Abstract
Stem cells are characterized by their self-renewal capacity and their ability to differentiate into multiple cell types of the human body. Using directed differentiation strategies, stem cells can now be converted into hepatocyte-like cells (HLCs) and therefore, represent a unique cell source for toxicological applications in vitro. However, the acquired hepatic functionality of stem cell-derived HLCs is still significantly inferior to primary human hepatocytes. One of the main reasons for this is that most in vitro models use traditional two-dimensional (2D) setups where the flat substrata cannot properly mimic the physiology of the human liver. Therefore, 2D-setups are progressively being replaced by more advanced culture systems, which attempt to replicate the natural liver microenvironment, in which stem cells can better differentiate towards HLCs. This review highlights the most recent cell culture systems, including scaffold-free and scaffold-based three-dimensional (3D) technologies and microfluidics that can be employed for culture and hepatic differentiation of stem cells intended for hepatotoxicity testing. These methodologies have shown to improve in vitro liver cell functionality according to the in vivo liver physiology and allow to establish stem cell-based hepatic in vitro platforms for the accurate evaluation of xenobiotics.
Keywords
Stem cells, Hepatocyte-like cells, 2D-and 3D-culture systems, In vitro toxicity, Drug screening, Microfluidics, HEPATOCYTE-LIKE CELLS, IN-VITRO DIFFERENTIATION, INDUCED LIVER-INJURY, HEPATIC DIFFERENTIATION, SHEAR-STRESS, DRUG TOXICITY, HEPATOGENIC DIFFERENTIATION, 3-DIMENSIONAL SCAFFOLDS, FUNCTIONAL HEPATOCYTES, EFFICIENT GENERATION

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MLA
Natale, Alessandra, et al. “Technological Advancements for the Development of Stem Cell-Based Models for Hepatotoxicity Testing.” ARCHIVES OF TOXICOLOGY, vol. 93, no. 7, 2019, pp. 1789–805, doi:10.1007/s00204-019-02465-y.
APA
Natale, A., Vanmol, K., Arslan, A., Van Vlierberghe, S., Dubruel, P., Van Erps, J., … Rodrigues, R. M. (2019). Technological advancements for the development of stem cell-based models for hepatotoxicity testing. ARCHIVES OF TOXICOLOGY, 93(7), 1789–1805. https://doi.org/10.1007/s00204-019-02465-y
Chicago author-date
Natale, Alessandra, Koen Vanmol, Aysu Arslan, Sandra Van Vlierberghe, Peter Dubruel, Jürgen Van Erps, Hugo Thienpont, et al. 2019. “Technological Advancements for the Development of Stem Cell-Based Models for Hepatotoxicity Testing.” ARCHIVES OF TOXICOLOGY 93 (7): 1789–1805. https://doi.org/10.1007/s00204-019-02465-y.
Chicago author-date (all authors)
Natale, Alessandra, Koen Vanmol, Aysu Arslan, Sandra Van Vlierberghe, Peter Dubruel, Jürgen Van Erps, Hugo Thienpont, Matij Buzgo, Joost Boeckmans, Joery De Kock, Tamara Vanhaecke, Vera Rogiers, and Robim M Rodrigues. 2019. “Technological Advancements for the Development of Stem Cell-Based Models for Hepatotoxicity Testing.” ARCHIVES OF TOXICOLOGY 93 (7): 1789–1805. doi:10.1007/s00204-019-02465-y.
Vancouver
1.
Natale A, Vanmol K, Arslan A, Van Vlierberghe S, Dubruel P, Van Erps J, et al. Technological advancements for the development of stem cell-based models for hepatotoxicity testing. ARCHIVES OF TOXICOLOGY. 2019;93(7):1789–805.
IEEE
[1]
A. Natale et al., “Technological advancements for the development of stem cell-based models for hepatotoxicity testing,” ARCHIVES OF TOXICOLOGY, vol. 93, no. 7, pp. 1789–1805, 2019.
@article{8614304,
  abstract     = {Stem cells are characterized by their self-renewal capacity and their ability to differentiate into multiple cell types of the human body. Using directed differentiation strategies, stem cells can now be converted into hepatocyte-like cells (HLCs) and therefore, represent a unique cell source for toxicological applications in vitro. However, the acquired hepatic functionality of stem cell-derived HLCs is still significantly inferior to primary human hepatocytes. One of the main reasons for this is that most in vitro models use traditional two-dimensional (2D) setups where the flat substrata cannot properly mimic the physiology of the human liver. Therefore, 2D-setups are progressively being replaced by more advanced culture systems, which attempt to replicate the natural liver microenvironment, in which stem cells can better differentiate towards HLCs. This review highlights the most recent cell culture systems, including scaffold-free and scaffold-based three-dimensional (3D) technologies and microfluidics that can be employed for culture and hepatic differentiation of stem cells intended for hepatotoxicity testing. These methodologies have shown to improve in vitro liver cell functionality according to the in vivo liver physiology and allow to establish stem cell-based hepatic in vitro platforms for the accurate evaluation of xenobiotics.},
  author       = {Natale, Alessandra and Vanmol, Koen and Arslan, Aysu and Van Vlierberghe, Sandra and Dubruel, Peter and Van Erps, Jürgen and Thienpont, Hugo and Buzgo, Matij and Boeckmans, Joost and De Kock, Joery and Vanhaecke, Tamara and Rogiers, Vera and Rodrigues, Robim M},
  issn         = {0340-5761},
  journal      = {ARCHIVES OF TOXICOLOGY},
  keywords     = {Stem cells,Hepatocyte-like cells,2D-and 3D-culture systems,In vitro toxicity,Drug screening,Microfluidics,HEPATOCYTE-LIKE CELLS,IN-VITRO DIFFERENTIATION,INDUCED LIVER-INJURY,HEPATIC DIFFERENTIATION,SHEAR-STRESS,DRUG TOXICITY,HEPATOGENIC DIFFERENTIATION,3-DIMENSIONAL SCAFFOLDS,FUNCTIONAL HEPATOCYTES,EFFICIENT GENERATION},
  language     = {eng},
  number       = {7},
  pages        = {1789--1805},
  title        = {Technological advancements for the development of stem cell-based models for hepatotoxicity testing},
  url          = {http://dx.doi.org/10.1007/s00204-019-02465-y},
  volume       = {93},
  year         = {2019},
}

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