Mechanical strain and BMP-stimulation instruct the extracellular matrix to control stem cell fate decisions: an age-dependent matrix code?

机械应变和 BMP 刺激指示细胞外基质控制干细胞命运决定：年龄依赖性基质代码？

• 批准号: 259402103
• 负责人: Professorin Dr. Petra Knaus
• 金额: --
• 依托单位: Berlin-Brandenburger Centrum für Regenerative Therapien (BCRT)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/259402103?language=en
• 关键词: Mechanical; strain; BMP; stimulation; instruct

Already in the very early phase of bone fracture healing, a complex extracellular matrix (ECM) network is assembled. The biochemical and mechanical signals provided by the ECM are believed to instruct cell fate and function. We hypothesize that the information encoded in the ECM is modulated by the physico-chemical stimuli present during its formation and that the stored information will be sensed by cells much longer than the stimuli were present. We will build ECM in 3D microtissue culture under control of mechanical straining and bone morphogenetic proteins (BMPs) and perform careful mechanical and biochemical characterization. We will furthermore study the instructiveness of decellularized matrices on bone progenitor cells and investigate the influence of ageing on the encoding and reading process. We propose that the ECM plays a relevant role as an age-dependent memory for mechanical and biochemical signals during bone regeneration.

在骨折愈合的非常早期阶段，已经组装了复杂的细胞外基质（ECM）网络。由ECM提供的生物化学和机械信号被认为指示细胞命运和功能。我们假设ECM中编码的信息在其形成过程中受到物理化学刺激的调制，并且存储的信息将被细胞感知的时间比刺激存在的时间长得多。我们将在机械应变和骨形态发生蛋白（BMP）的控制下，在3D微组织培养中构建ECM，并进行仔细的机械和生物化学表征。我们将进一步研究脱细胞基质对骨祖细胞的粘附性，并调查老化对编码和阅读过程的影响。我们认为，ECM在骨再生过程中作为机械和生化信号的年龄依赖性记忆发挥着相关作用。