Motility behavior of hepatocytes on extracellular matrix substrata during aggregation

Powers, Mark J.; Griffith, Linda G.

doi:10.1002/(sici)1097-0290(19960520)50:4<392::aid-bit6>3.0.co;2-g

Cited by 43 publications

(16 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results show that strong cell-ECM adhesion results in the formation of larger numbers of smaller aggregates, and increases the time taken for aggregates to form. Our results agree with experimental findings reported in Powers and Griffith-Cima (1996), that strong cell-substrate adhesion inhibits migration, and are consistent with the hypothesis that aggregates do not form when cell-ECM adhesions are stronger than cell contractile forces. When cell-ECM adhesion is extremely strong, we found cell movement was almost completely eliminated, which reproduces the experimental findings of Riccalton-Banks (2002) for cells seeded on tissue culture plastic.…”

Section: Discussionsupporting

confidence: 93%

“…It is well known that both the strength of cell-ECM adhesion and the material properties of the ECM contribute significantly to cell mobility (Powers and Griffith-Cima, 1996;Thomas and DiMilla, 2000). Our results show that strong cell-ECM adhesion results in the formation of larger numbers of smaller aggregates, and increases the time taken for aggregates to form.…”

Section: Discussionsupporting

confidence: 49%

“…These aggregates then detach themselves from the surface of the ECM and reorganise to form multicellular spheroids, the diameter of which is around 100-150 µm (Thomas et al, 2005), as we can see from Fig. 1 (compared to a representative cell diameter of 10-30 µm (Higuchi and Tsukamoto, 2004;Glicklis et al, 2000)). The migration of hepatocytes during the early stages of aggregation is described in detail in Powers and Griffith-Cima (1996). They found that only around 6 % of observed cells exhibited 'classical single-cell locomotion', defined as occurring when a cell translates one body length, without contacting another cell.…”

Section: Riccalton-banks)mentioning

confidence: 99%

“…The viscous effects are intended to capture the tendency of cells to align and match their velocities with the local average cell velocity (Babak et al, 2004). In the context of liver cell aggregation, the viscous term represents migration of hepatocytes as coupled pairs or groups (Powers and Griffith-Cima, 1996). Obviously, cells differ from viscous fluids in that they are able to generate forces in response to cues from their environment, such as variations in the local cell density.…”

Section: Constitutive Relationsmentioning

confidence: 99%

See 3 more Smart Citations

A Mathematical Model of Liver Cell Aggregation In Vitro

et al. 2008

View full text Add to dashboard Cite

"Authors may self-archive the author's accepted manuscript of their articles on their own websites. Authors may also deposit this version of the article in any repository, provided it is only made publicly available 12 months after official publication or later. He/ she may not use the publisher's version (the final article), which is posted on SpringerLink and other Springer websites, for the purpose of self-archiving or deposit. Furthermore, the author may only post his/her version provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com"". th March, 2014A mathematical model of liver cell aggregation in vitroThe behaviour of mammalian cells within three-dimensional structures is an area of intense biological research and underpins the efforts of tissue engineers to regenerate human tissues for clinical applications. In the particular case of hepatocytes (liver cells), the formation of spheroidal multicellular aggregates has been shown to improve cell viability and functionality compared to traditional monolayer culture techniques.We propose a simple mathematical model for the early stages of this aggregation process, when cell clusters form on the surface of the extracellular matrix (ECM) layer on which they are seeded. We focus on interactions between the cells and the viscoelastic ECM substrate. Governing equations for the cells, culture medium and ECM are derived using the principles of mass and momentum balance. The model is then reduced to a system of four partial differential equations, which are investigated analytically and numerically. The model predicts that, provided cells are seeded at a suitable density, aggregates with clearly defined boundaries and a spatially uniform cell density on the interior will form. While the mechanical properties of the ECM do not appear to have a significant effect, strong cell-ECM interactions can inhibit, or possibly prevent, the formation of aggregates. The paper concludes with a discussion of our key findings and suggestions for future work.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 49%

Section: Riccalton-banks)mentioning

confidence: 99%

Section: Constitutive Relationsmentioning

confidence: 99%

See 2 more Smart Citations

A Mathematical Model of Liver Cell Aggregation In Vitro

et al. 2008

View full text Add to dashboard Cite

show abstract

“…62 In addition, although cellular response to RGD can depend on how the peptide is presented (e.g., clustering density 63 ), we have conjugated RGDS to 10% PEG-DA hepatocyte-laden hydrogels using the same copolymerization route in the past. 15 That RGDS was not necessary for optimal hepatocyte function in the present case may be due to cross-talk between cell-matrix and cellcell interaction pathways, [64][65][66] and suggests that cell-cell contacts established during the 2D phase of microtissue construction were sufficient to alleviate the need for any cell-matrix contacts in 3D, as the PEG hydrogel background is biologically inert. Alternatively, it is possible that despite collagenase digestion, secreted ECM molecules remain attached to hepatocytes and are subsequently immobilized during encapsulation.…”

Section: Characterization Of Microtissue Drug Metabolism Enzyme Activitymentioning

confidence: 99%

Micropatterned Cell–Cell Interactions Enable Functional Encapsulation of Primary Hepatocytes in Hydrogel Microtissues

Stevens

Schwartz

et al. 2014

Tissue Engineering Part A

123

View full text Add to dashboard Cite

Drug-induced liver injury is a major cause of drug development failures and postmarket withdrawals. In vitro models that incorporate primary hepatocytes have been shown to be more predictive than model systems which rely on liver microsomes or hepatocellular carcinoma cell lines. Methods to phenotypically stabilize primary hepatocytes ex vivo often rely on mimicry of hepatic microenvironmental cues such as cell-cell interactions and cell-matrix interactions. In this work, we sought to incorporate phenotypically stable hepatocytes into threedimensional (3D) microtissues, which, in turn, could be deployed in drug-screening platforms such as multiwell plates and diverse organ-on-a-chip devices. We first utilize micropatterning on collagen I to specify cell-cell interactions in two-dimensions, followed by collagenase digestion to produce well-controlled aggregates for 3D encapsulation in polyethylene glycol (PEG) diacrylate. Using this approach, we examined the influence of homotypic hepatocyte interactions and composition of the encapsulating hydrogel, and achieved the maintenance of liver-specific function for over 50 days. Optimally preaggregated structures were subsequently encapsulated using a microfluidic droplet-generator to produce 3D microtissues. Interactions of engineered hepatic microtissues with drugs was characterized by flow cytometry, and yielded both induction of P450 enzymes in response to prototypic small molecules and drug-drug interactions that give rise to hepatotoxicity. Collectively, this study establishes a pipeline for the manufacturing of 3D hepatic microtissues that exhibit stabilized liver-specific functions and can be incorporated into a wide array of emerging drug development platforms.

show abstract

Adhesion-guided in vitro morphogenesis in pure and mixed cell cultures

Powers

Griffith

1998

Microsc. Res. Tech.

View full text Add to dashboard Cite

Motility behavior of hepatocytes on extracellular matrix substrata during aggregation

Cited by 43 publications

References 42 publications

A Mathematical Model of Liver Cell Aggregation In Vitro

A Mathematical Model of Liver Cell Aggregation In Vitro

Micropatterned Cell–Cell Interactions Enable Functional Encapsulation of Primary Hepatocytes in Hydrogel Microtissues

Adhesion-guided in vitro morphogenesis in pure and mixed cell cultures

Contact Info

Product

Resources

About