A mathematical model for lymphangiogenesis in normal and diabetic wounds
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Publication:739416
DOI10.1016/J.JTBI.2015.07.023zbMATH Open1343.92062arXiv1501.00421OpenAlexW1574159934WikidataQ38413201 ScholiaQ38413201MaRDI QIDQ739416FDOQ739416
Arianna Bianchi, Jonathan A. Sherratt, Kevin J. Painter
Publication date: 18 August 2016
Published in: Journal of Theoretical Biology (Search for Journal in Brave)
Abstract: Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis) very few have been proposed for the regeneration of the lymphatic network. Moreover, lymphangiogenesis is markedly distinct from angiogenesis, occurring at different times and in a different manner. Here a model of five ordinary differential equations is presented to describe the formation of lymphatic capillaries following a skin wound. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from experimental and clinical data. The system is then solved numerically and the results are compared with the available biological literature. Finally, a parameter sensitivity analysis of the model is taken as a starting point for suggesting new therapeutic approaches targeting the enhancement of lymphangiogenesis in diabetic wounds. The work provides a deeper understanding of the phenomenon in question, clarifying the main factors involved. In particular, the balance between TGF- and VEGF levels, rather than their absolute values, is identified as crucial to effective lymphangiogenesis. In addition, the results indicate lowering the macrophage-mediated activation of TGF- and increasing the basal lymphatic endothelial cell growth rate, emph{inter alia}, as potential treatments. It is hoped the findings of this paper may be considered in the development of future experiments investigating novel lymphangiogenic therapies.
Full work available at URL: https://arxiv.org/abs/1501.00421
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