Evaluation of xenogeneic extracellular matrix fabricated from CuCl2-conditioned mesenchymal stem cell sheets as a bioactive wound dressing material
Evaluation of xenogeneic extracellular matrix fabricated from CuCl2-conditioned mesenchymal stem cell sheets as a bioactive wound dressing material
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CuCl2 条件间充质干细胞片异种细胞外基质作为生物活性伤口敷料材料的评价
DOI：
10.1177/0885328217731951
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
李立文
中科院分区：
文献类型：
--
作者：
都慧聪;姜琳;耿文鑫;李靖;张锐;党金鸽;舒茂国;李立文
细胞外基质不仅作为生物活性的三维支架材料，而且通过提供生化信号来调节细胞的行为，在组织工程领域引起了人们的极大兴趣。基于细胞外基质的生物材料主要来源于异种组织，在促进皮肤创面愈合方面显示出积极的效果。然而，这种细胞外基质只含有低剂量的生长因子，这限制了它们的治疗效率。最近的报道表明，由间充质干细胞制成的细胞片可以通过促进再上皮化和血管生成来加速创面修复，但其临床移植受到一些限制，如异常免疫反应的风险和成本问题。在这项研究中，从CuCl2条件下的骨髓间充质干细胞片材中制备了脱细胞细胞外基质，并在小鼠全层皮肤缺损模型中评估了它们的体内伤口愈合性能。我们发现，由CuCl2条件下的间充质干细胞片衍生的细胞外基质具有致密的表面和厚的固体样的横截面结构。此外，CuCl2通过低氧诱导因子-1α的激活，显著丰富细胞外基质中的I型胶原、III型胶原、转化生长因子-1、血管内皮生长因子和碱性成纤维细胞生长因子。因此，通过早期脂肪细胞动员、促进肉芽组织形成、快速再上皮化和增强血管生成，所产生的细胞外基质在体内显示出显著的改善伤口愈合的能力。因此，我们认为从CuCl2条件下的间充质干细胞片材获得的细胞外基质具有临床转译的潜力，并可能导致一种新的伤口处理策略。
The extracellular matrix has drawn considerable interest in tissue engineering not only acts as a bioactive three-dimensional scaffold but also regulates cell behaviors through providing biochemical signals. Extracellular matrix-based biomaterials, mainly derived from xenogeneic tissues, have shown positive outcomes in promoting cutaneous wound healing. However, such extracellular matrices only contain low doses of growth factors, which limit their therapeutic efficiency. Recent reports demonstrated that cell sheets made from mesenchymal stem cell can accelerate wound repair through enhanced re-epithelialization and angiogenesis, but its clinical translation is hindered by several limitations, such as the risk of aberrant immune responses and cost implications. In this study, acellular extracellular matrices were prepared from CuCl2-conditioned mesenchymal stem cell sheets and their in vivo wound healing properties were evaluated in a mouse model of full-thickness skin defect. We found that extracellular matrices derived from CuCl2-conditioned mesenchymal stem cell sheets have a compact surface with thick solid-like cross-sectional structure. Moreover, CuCl2 dramatically enriched the extracellular matrices with collagen I, collagen III, transforming growth factor-β1, vascular endothelial growth factor, and basic fibroblast growth factor via hypoxia-inducible factor-1α activation. And as a consequence, the resulting extracellular matrices showed markedly improved in vivo wound healing potency through early adipocyte mobilization, enhanced granulation tissues formation, rapid re-epithelialization, and augmented angiogenesis. Therefore, we consider that the extracellular matrix derived from CuCl2-conditioned mesenchymal stem cell sheets has the potential for clinical translation and may lead to a novel strategy for wound management.
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