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
RESTORE Research Center, Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT, Toulouse, France.
Sorbonne Université, Inria Paris, Université de Paris, CNRS, team MUSCLEES, Laboratoire Jacques-Louis Lions, UMR7598, Paris, France.
NPJ Regen Med. 2024 Oct 15;9(1):29. doi: 10.1038/s41536-024-00373-z.
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.
哺乳动物出生后再生效率的下降是组织修复再生医学的一个重大障碍。我们之前开发了一种基于计算代理的模型（ABM），该模型概括了细胞与细胞外基质（ECM）之间的机械相互作用，以研究成年组织修复的关键驱动因素。该模型的时间校准以及参数敏感性分析表明，ECM交联的早期短暂减少引导组织修复走向再生。与计算模型一致，成年小鼠皮下脂肪组织（AT）切除后的头六天，对纤维交联进行短暂抑制或刺激分别导致再生或瘢痕愈合。因此，这项工作将计算模型定位为组织再生的预测工具，随着进一步发展，它将成为我们体内模型的数字孪生体。此外，它还开辟了针对ECM交联以诱导成年哺乳动物组织再生的新治疗方法。
