A computational model reveals an early transient decrease in fiber cross-linking that unlocks adult regeneration

The decline in regeneration efficiency after birth in mammals is a significant roadblock for regenerative medicine in tissue repair. We previously developed a computational agent based-model (ABM) that recapitulates mechanical interactions between cells and the extracellular-matrix (ECM), to investi...

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Published in:npj Regenerative medicine 2024-10, Vol.9 (1), p.29-9, Article 29
Main Authors: Pacary, Anastasia, Peurichard, Diane, Vaysse, Laurence, Monsarrat, Paul, Bolut, Clémence, Girel, Adeline, Guissard, Christophe, Lorsignol, Anne, Planat-Benard, Valérie, Paupert, Jenny, Ousset, Marielle, Casteilla, Louis
Format: Article
Language:English
Subjects:
631/443
631/80
Adipocytes
Biomaterials
Biomedical and Life Sciences
Biomedicine
Body fat
Cell Biology
Hypotheses
Immunology
Life Sciences
Regenerative medicine
Regenerative Medicine/Tissue Engineering
Scars
Sensitivity analysis
Stem Cells
Tissue engineering
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Summary:The decline in regeneration efficiency after birth in mammals is a significant roadblock for regenerative medicine in tissue repair. We previously developed a computational agent based-model (ABM) that recapitulates mechanical interactions between cells and the extracellular-matrix (ECM), to investigate key drivers of tissue repair in adults. Time calibration alongside a parameter sensitivity analysis of the model suggested that an early and transient decrease in ECM cross-linking guides tissue repair toward 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 with further development will behave 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.
ISSN:2057-3995
2057-3995
DOI:10.1038/s41536-024-00373-z