Photo of Dr. Heindryckx in front of work bench

Femke Heindryckx, Uppsala University, Medical Cell Biology

 

 

 

 

  

 

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The Role of the Tumor Environment on Hepatocellular Carcinoma

Research Interest

The research group of Pär Gerwins and Femke Heindryckx studies the role of the fibrotic tumor environment in the progression of hepatocellular carcinoma, using models that mimic liver fibrosis and liver cancer1. Throughout our projects, we focus on different hallmarks of the fibrotic environment that could influence tumor growth2. One of the key cell types in our research are fibroblasts and hepatic stellate cells, on which we study their activation towards the contractile collagen producing myofibroblast. By identifying factors that prevent or revert the activation of fibroblasts and stellate cells, we hope to reduce fibrosis and eventually hepatocellular carcinoma. Recently we found that targeting of ER stress-induced signaling might be a therapeutic strategy to fight fibrotic diseases3.

  

The Experiment

The microfluidic CellDirector® 2D assay (Gradientech) is used to study cellular migration to platelet-derived growth factor (PDGF) of diseased human lung fibroblasts isolated from adult lung tissue of cystic fibrosis patients (HLF-CF). A continuous flow of cell media, as well as cell media containing PDGF, exposes the cells to a stable gradient throughout the entire experiment. By following cell responses in realtime, true chemotaxis can be distinguished from random cell migration. The cell responses are followed over time by real-time imaging using the CytoSMART™ System. In order to quantify chemotaxis, images are analyzed by the cell tracking software Tracking Tool™ PRO.

 

Video of chemotaxis of disease HLF-CF growing in CellDirector® 2D recorded with the CytoSMART™ Lux 10X Device (Snapshot interval: 7.5 minutes)  

Analysis of CytoSMART™ Video by the Tracking Tool™ PRO cell tracking software (Gradientech). Cell trajectory of three experiments was plotted on a merged polar coordinate grid.


Conclusion

The CytoSMART™ System in combination with the CellDirector® 2D Microfluidic Assay constitute a cost-effective and easy-to-use solution for performing high-quality cell migration experiments of physiological relevance. By monitoring the cells in-real time in conditions of stable and controllable chemoattractant gradients, true chemotaxis can be distinguished from random chemokinesis. By comparing migration velocities of cells exposed to a gradient of a chemoattractant, with the velocities of cells in the positive and negative control channels, chemotaxis can easily be distinguished from pure chemokinetic responses. To summarize, the large field of view of the CytoSMART™ System allows for real-time imaging of gradient and control conditions within the CellDirector® 2D Assay, constituting a markedly less expensive solution compared to regular time-lapse microscopes with movable stages.

 

References

  1. Heindryckx F, Colle I, Van Vlierberghe H (2009) International Journal of Experimental Pathology, 90; 367-386

  2. Heindryckx F, Gerwins P (2015) World Journal of Hepatology 7:165-76

  3. Heindryckx F, Binet F, Ponticos M, Rombouts K, Kreuger J et al. (2016). EMBO Molecular Medicine, 8; 729–744

 

Find out more about Dr. Heindryckx research.

Interested to present your research here? Then apply to become a CytoSMART™ Lab. You will receive a CytoSMART™ System on loan for 4 weeks and your project will be featured on the Lonza website.

 

How to become a CytoSMART™ Lab