BB22: Lymphaniogenesis and vasculogenesis: the interplay between biophysical and biochemical stimuli in network development
| Researcher: | Dr Chris Bell |
| Team Leader(s): | Dr Sarah Waters, Prof. 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
