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首页> 外文期刊>RSC Advances >MSCs on an acellular dermal matrix (ADM) sourced from neonatal mouse skin regulate collagen reconstruction of granulation tissue during adult cutaneous wound healing
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MSCs on an acellular dermal matrix (ADM) sourced from neonatal mouse skin regulate collagen reconstruction of granulation tissue during adult cutaneous wound healing

机译：来自新生小鼠皮肤的脱细胞真皮基质（ADM）上的MSC在成年皮肤伤口愈合过程中调节肉芽组织的胶原蛋白重建

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Full-thickness cutaneous wound repair in adults usually leads to non-regenerative healing, which produces disorganized and non-functional fibrotic tissues. Mesenchymal stem cells (MSCs) on acellular dermal matrix (ADM) scaffolds are currently believed to be a promising strategy for wound healing improvement. Extracellular matrix (ECM) is aware of playing a pivotal role in wound healing, and changing the properties of the ECM is therefore expected to alter repair outcomes. Inspired by the analogous regeneration process in foetal skin with minimal or no scar tissue formation, in this study, ADM scaffold sourced from 1 day old mouse skin is introduced. Its influence on collagen reconstruction of granulation tissue during adult full-thickness wound healing is revealed and is compared to that from 20 week old mouse skin. Advanced nonlinear optical two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging were used to intravitally and three-dimensionally monitor the activities of MSCs and formation of granulation tissue. Dynamic changes of collagen content in granulation tissue were analyzed from aspects of synthesis and degradation. The associated collagen proteins, type I and type III collagen (Col-I and Col-III) and matrix matalloproteinase-13 (Mmp-13) were assessed at the transcriptional, translational and deposition levels. The results showed that there were significant differences in remodelling characteristics as a consequence of ADM properties. One-day old ADM + MSC treatment induced up-regulation of Col-III expression, down-regulation of Col-I and also down-regulation of Mmp-13. Accordingly, 1 day ADM + MSC treatment caused higher type III collagen deposition and a higher ratio of Col-III/Col-I in the granulation tissue. ADM derived from 1 day old skin ECM was superior to ADM derived from 20 week old skin ECM, caused enhanced angiogenesis, down regulation of TGF-β1 and promoted re-epithelization and faster, more constructive, and compositionally appropriate formation of granulation tissue. These results suggest that ADM derived from 1 day old skin ECM is a favourable biomaterial for adult wound healing.
机译：在成年人中，全层皮肤伤口修复通常会导致非再生性愈合，从而产生混乱且无功能的纤维化组织。无细胞真皮基质（ADM）支架上的间充质干细胞（MSC）目前被认为是改善伤口愈合的一种有前途的策略。细胞外基质（ECM）意识到在伤口愈合中起着举足轻重的作用，因此改变ECM的性质有望改变修复效果。受胎儿皮肤中具有很少或没有疤痕组织形成的类似再生过程的启发，在这项研究中，引入了源自1日龄小鼠皮肤的ADM支架。揭示了其对成年全层伤口愈合过程中肉芽组织胶原重建的影响，并将其与20周龄小鼠皮肤的影响进行了比较。先进的非线性光学双光子荧光（TPF）和二次谐波生成（SHG）成像用于活体内和三维监测MSCs的活动和肉芽组织的形成。从合成和降解方面分析了肉芽组织中胶原含量的动态变化。在转录，翻译和沉积水平上评估了相关的胶原蛋白，I型和III型胶原蛋白（Col-I和Col-III）和基质金属蛋白酶13（Mmp-13）。结果表明，由于ADM特性，重塑特性存在显着差异。一天的老ADM + MSC处理诱导了Col-III表达的上调，Col-I的下调以及Mmp-13的下调。因此，1天的ADM + MSC处理导致肉芽组织中更高的III型胶原蛋白沉积和更高的Col-III / Col-1比率。源自1天龄皮肤ECM的ADM优于源自20周龄皮肤ECM的ADM，可引起增强的血管生成，下调TGF-β1并促进重新上皮，并更快，更具建设性且在结构上适合肉芽组织形成。这些结果表明，源自1日龄皮肤ECM的ADM是成人伤口愈合的有利生物材料。

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