BB22: Lymphaniogenesis and vasculogenesis: the interplay between biophysical and biochemical stimuli in network development

Researcher:  Dr Chris Bell
Team Leader(s): Dr Sarah WatersProf. Helen Byrne & Dr Jonathan Whiteley
Collaborators: Prof. Melody Swartz, EPFL
Prof. Luigi Preziosi, Politecnico di Torino

Background

Lymphangiogenesis and vasculogenesis are the de novo formation of networks of lymph and blood vessels from lymph endothelial cells (LECs) and blood endothelial cells (BECs), respectively. Recent experimental investigations [1] have identified three major biophysical and biochemical factors that influence lymph and blood network formation from their constituent cells: interstitial flow, the composition of the extracellular matrix and the spatial distribution of vascular endothelial growth factor. Theoretical insights into the influence of each of these factors will have significant implications for in vitro tissue engineering, and for the understanding of in vivo processes, e.g. wound healing.

Techniques and Challenges

We are currently developing new multiphase continuum models, which will account for the effects of the three factors described above. A review of extant vasculogenesis models is given in [2]. Initially, we are considering separately the formation of lymph networks and blood networks, since experimental data indicates that their cells respond differently to the factors. Model parameters will be estimated from data that is generated in the laboratory.  Analysis of the model equations and their validation against the experimental data will reveal whether the biophysical mechanisms included in the models are sufficient to reproduce the observed experimental phenomena, or whether further refinements are required.

Results

The project is in its initial stages and results will be reported as they are obtained.

The Future

After developing separate models for lymphatic and blood vascular networks, we intend to model the simultaneous formation of both networks from a matrix seeded with LECs and BECs. The synergies obtained from the parallel development of mathematical models and experiments will significantly improve our understanding of coordinated network growth in tissues.

References

[1] Helm C-L.E., Zisch A., Swartz M.A., Engineered blood and lymphatic capillaries in 3-D VEGF-Fibrin-Collagen matrices with interstitial flow, Biotechnol. Bioeng. 96, 167, 2007

[2] Ambrosi D., Bussolino F., Preziosi L., A review of vasculogenesis models, J. Theor. Med. 6, 1, 2005