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

IF 6.4 1区医学 Q1 CELL & TISSUE ENGINEERING

npj Regenerative Medicine Pub Date : 2024-10-15 DOI:10.1038/s41536-024-00373-z

Anastasia Pacary, Diane Peurichard, Laurence Vaysse, Paul Monsarrat, Clémence Bolut, Adeline Girel, Christophe Guissard, Anne Lorsignol, Valérie Planat-Benard, Jenny Paupert, Marielle Ousset, Louis Casteilla

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引用次数: 0

Abstract

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.

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一个计算模型揭示了纤维交联的早期瞬时减少，从而开启了成体再生。

哺乳动物出生后再生效率的下降是再生医学在组织修复方面的一大障碍。我们之前开发了一种基于代理的计算模型（ABM），该模型再现了细胞与细胞外基质（ECM）之间的机械相互作用，以研究成人组织修复的关键驱动因素。该模型的时间校准和参数敏感性分析表明，ECM 交联的早期和瞬时减少会引导组织修复走向再生。与计算模型一致的是，在成年小鼠皮下脂肪组织（AT）切除后的前六天，纤维交联的瞬时抑制或刺激分别导致了再生或疤痕愈合。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。此外，它还为针对 ECM 交联诱导成年哺乳动物组织再生开辟了新的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

npj Regenerative Medicine Engineering-Biomedical Engineering

CiteScore

10.00

自引率

1.40%

发文量

审稿时长

12 weeks

期刊介绍： Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.