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Project aims:
We investigate the mechanisms by which adipose tissues reconstruct after injury. By extending the morphogenesis model [1] to account for tissue reconstruction (ECM insemination, inflammation phase), we show that the model successfully generates regeneration or scar formation as functions of few key parameters, and seems to indicate that the fate of injury outcome could be mainly due to ECM rigidity (crosslink amount and remodelling speed) [2].
Based on these model predictions, we perform a combined in-vivo / in-silico study by interfacing model simulations to experiments on mice tissues.
We discover in-silico that a transient an early decrease in ECM cross-linking guides tissue repair towards regeneration. Consistent with the computational model, transient inhibition or stimulation of fiber cross-linking for the first six days after subcutaneous adipose tissue (AT) resection in adult mice led to regenerative or scar healing, respectively. Therefore, this work positions the computational model as a predictive tool for tissue regeneration that behaves as a digital twin of our in vivo model. In addition, it opens new therapeutic approaches targeting ECM cross-linking to induce tissue regeneration in adult mammals.
Collaborations:
A. Pacary, J. Paupert, A. Lorsignol, M. Ousset, L. Casteilla (RESTORE, Toulouse)
P. Degond (IMT, Toulouse)
Related publications:
D. Peurichard, F. Delebecque, A. Lorsignol, C. Barreau, J. Rouquette , X. Descombes, L. Casteilla and P. Degond, Simple mechanical cues could explain adipose tissue morphology, Journal of Theoretical Biology (2017). https://doi.org/10.1016/j.jtbi.2017.06.030
D. Peurichard, M. Ousset, J. Paupert, B. Aymard, A. Lorsignol, L. Casteilla, P. Degond, Extra-cellular matrix rigidity may dictate the fate of injury outcome, Journal of Theoretical Biology 469 (2019), pp. 127-136.
A. Pacary, D. Peurichard, L. Vaysse, P. Montsarrat, C. Bolut, A. Girel, C. Guissard, A. Lorsignol, V. Planat, J. Paupert, M. Ousset, L. Casteilla, A digital tissue repair model identifies an early transient decrease in fiber cross-linking that unlocks regeneration in adult mammals, NPJ Regen Med 9, 29 (2024), link
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