The fibrotic response of primary liver spheroids recapitulates in vivo hepatic stellate cell activation

Mannaerts, Inge; Eysackers, Nathalie; Os, Elise Anne van; Verhulst, Stefaan; Roosens, T.; Smout, Ayla; Hierlemann, Andreas; Frey, Olivier; Leite, Sofia Batista; Grunsven, Leo A. van

doi:10.1016/j.biomaterials.2020.120335

Cited by 23 publications

(22 citation statements)

References 56 publications

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“…This is due to the cellular organisation and fluid flow not being captured as realistically in 2-D systems as it is in 3-D systems. [21][22][23][24] These more-relevant systems can take the form of 3-D spheroids, bioreactors, microphysiological systems (MPS) and organon-a-chip (OoC), among others. 25,26 The VCBA model consists of four sub-models (Figure 1):…”

Section: Introductionmentioning

confidence: 99%

Extension of the Virtual Cell Based Assay from a 2-D to a 3-D Cell Culture Model

Bednarczyk

Paini

et al. 2022

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Prediction of chemical toxicity is very useful in risk assessment. With the current paradigm shift towards the use of in vitro and in silico systems, we present herein a theoretical mathematical description of a quasi-diffusion process to predict chemical concentrations in 3-D spheroid cell cultures. By extending a 2-D Virtual Cell Based Assay (VCBA) model into a 3-D spheroid cell model, we assume that cells are arranged in a series of concentric layers within the sphere. We formulate the chemical quasi-diffusion process by simplifying the spheroid with respect to the number of cells in each layer. The system was calibrated and tested with acetaminophen (APAP). Simulated predictions of APAP toxicity were compared with empirical data from in vitro measurements by using a 3-D spheroid model. The results of this first attempt to extend the VCBA model are promising — they show that the VCBA model simulates close correlation between the influence of compound concentration and the viability of the HepaRG 3-D cell culture. The 3-D VCBA model provides a complement to current in vitro procedures to refine experimental setups, to fill data gaps and help in the interpretation of in vitro data for the purposes of risk assessment.

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Section: Introductionmentioning

confidence: 99%

Extension of the Virtual Cell Based Assay from a 2-D to a 3-D Cell Culture Model

Bednarczyk

Paini

et al. 2022

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“…Wu et al 92 established a non-alcoholic fatty liver disease (NAFLD) model through perfusion culture of HepG2 cells in decellularized liver scaffolds, which provided a useful tool for studying the development of NAFLD in vitro and screening relevant drugs. Co-culture of hepatocytes and hepatic stellate cells as cell aggregates has also been recently reported by Coll et al 69 and Mannaerts et al 93 for modeling of liver fibrosis in vitro. Although various strategies have been reported for liver tissue engineering and regeneration, the most promising approaches are based on cell aggregates and decellularized liver scaffolds due to their replication of physiological liver structures.…”

Section: Bioengineering Of Functional Hepatic Constructsmentioning

confidence: 62%

Stem cell therapy and tissue engineering strategies using cell aggregates and decellularized scaffolds for the rescue of liver failure

et al. 2021

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Liver failure is a lethal condition with hepatocellular dysfunction, and liver transplantation is presently the only effective treatment. However, due to the limited availability of donors and the potential immune rejection, novel therapeutic strategies are actively sought to restore the normal hepatic architectures and functions, especially for livers with inherited metabolic dysfunctions or chronic diseases. Although the conventional cell therapy has shown promising results, the direct infusion of hepatocytes is hampered by limited hepatocyte sources, poor cell viability, and engraftment. Hence, this review mainly highlights the role of stem cells and progenitors as the alternative cell source and summarizes the potential approaches based on tissue engineering to improve the delivery efficiency of cells. Particularly, the underlying mechanisms for cell therapy using stem cells and progenitors are discussed in two main aspects: paracrine effect and cell differentiation. Moreover, tissue-engineering approaches using cell aggregates and decellularized liver scaffolds for bioengineering of functional hepatic constructs are discussed and compared in terms of the potential to replicate liver physiological structures. In the end, a potentially effective strategy combining the premium advantages of stem cell aggregates and decellularized liver scaffolds is proposed as the future direction of liver tissue engineering and regeneration.

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“…The differentiation of hepatic stellate cells (HSCs) into collagen-secreting myofibroblasts activates fibrosis, as does hepatocyte (HEP) damage. HSC/HEP cell spheroids are used to test drugs that may counter fibrosis, as the spheroids exhibit in vivo -like HSC behavior 82 .…”

Section: Spheroid Applications In Tementioning

confidence: 99%

The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications

et al. 2021

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A spheroid is a complex, spherical cellular aggregate supporting cell-cell and cell-matrix interactions in an environment that mimics the real-world situation. In terms of tissue engineering, spheroids are important building blocks that replace two-dimensional cell cultures. Spheroids replicate tissue physiological activities. The use of spheroids with/without scaffolds yields structures that engage in desired activities and replicate the complicated geometry of three-dimensional tissues. In this mini-review, we describe conventional and novel methods by which scaffold-free and scaffolded spheroids may be fabricated and discuss their applications in tissue regeneration and future perspectives.

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The fibrotic response of primary liver spheroids recapitulates in vivo hepatic stellate cell activation

Cited by 23 publications

References 56 publications

Extension of the Virtual Cell Based Assay from a 2-D to a 3-D Cell Culture Model

Extension of the Virtual Cell Based Assay from a 2-D to a 3-D Cell Culture Model

Stem cell therapy and tissue engineering strategies using cell aggregates and decellularized scaffolds for the rescue of liver failure

The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications

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