Differential Response of Human Adipose Tissue-Derived Mesenchymal Stem Cells, Dermal Fibroblasts, and Keratinocytes to Burn Wound Exudates: Potential Role of Skin-Specific Chemokine CCL27
Differential Response of Human Adipose Tissue-Derived Mesenchymal Stem Cells, Dermal Fibroblasts, and Keratinocytes to Burn Wound Exudates: Potential Role of Skin-Specific Chemokine CCL27
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DOI：
10.1089/ten.tea.2013.0123
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发表时间：
2014-01-01
影响因子：
4.1
通讯作者：
Gibbs, Susan
中科院分区：
文献类型：
--
作者：
van den Broek, Lenie J.;Kroeze, Kim L.;Gibbs, Susan
目前正在探索许多基于细胞的再生医学策略，以实现组织工程构建。细胞间相互作用和与不同生物材料的相互作用被广泛研究，然而很少有研究涉及移植后培养细胞如何与存在于伤口床内的可溶性伤口愈合介质相互作用。本研究的目的是确定脂肪组织来源的间充质干细胞（ASC）、真皮成纤维细胞和角化细胞在与皮肤烧伤创面接触时的反应。深烧伤创面渗出液中含有多种细胞因子，包括与炎症和创面愈合相关的趋化因子和生长因子。ELISA法鉴定了17种介质（浓度范围0.0006 ~ 9 ng/mg总蛋白），其中包括皮肤特异性趋化因子CCL27。烧伤创面渗出液能激活ASC和真皮成纤维细胞，但不能激活角质形成细胞，从而增加CXCL1、CXCL8、CCL2和CCL20的分泌。值得注意的是，ASC而非成纤维细胞或角化细胞显示血管内皮生长因子（5倍）和白细胞介素- 6（253倍）的分泌显著增加，尽管当细胞掺入双层皮肤替代品（SS）时，这些差异不那么明显。当用重组人- ccl27代替烧伤创面渗出液时，观察到ASC和真皮成纤维细胞单培养物之间存在类似的差异。尽管CCL27没有刺激角质形成细胞分泌任何伤口愈合介质，但与ASC或真皮成纤维细胞相比，这些细胞表现出增加的增殖和迁移。综上所述，这些结果表明，在移植中，角化细胞主要被激活以促进伤口愈合。相反，真皮成纤维细胞，尤其是ASC对存在于伤口床的因子反应强烈，导致血管生成/肉芽组织形成因子的分泌增加。我们的研究结果对再生医学策略中使用的细胞类型（ASC或真皮成纤维细胞）的选择具有启示意义，并表明在开发难以愈合的皮肤伤口的先进疗法时考虑与伤口床的相互作用的重要性。
Many cell-based regenerative medicine strategies toward tissue-engineered constructs are currently being explored. Cell-cell interactions and interactions with different biomaterials are extensively investigated, whereas very few studies address how cultured cells will interact with soluble wound-healing mediators that are present within the wound bed after transplantation. The aim of this study was to determine how adipose tissue-derived mesenchymal stem cells (ASC), dermal fibroblasts, and keratinocytes will react when they come in contact with the deep cutaneous burn wound bed. Burn wound exudates isolated from deep burn wounds were found to contain many cytokines, including chemokines and growth factors related to inflammation and wound healing. Seventeen mediators were identified by ELISA (concentration range 0.0006-9 ng/mg total protein), including the skin-specific chemokine CCL27. Burn wound exudates activated both ASC and dermal fibroblasts, but not keratinocytes, to increase secretion of CXCL1, CXCL8, CCL2, and CCL20. Notably, ASC but not fibroblasts or keratinocytes showed significant increased secretion of vascular endothelial growth factor (5-fold) and interleukin- 6 (253-fold), although when the cells were incorporated in bi-layered skin substitute (SS) these differences were less pronounced. A similar discrepancy between ASC and dermal fibroblast mono-cultures was observed when recombinant human-CCL27 was used instead of burn wound exudates. Although CCL27 did not stimulate the secretion of any of the wound-healing mediators by keratinocytes, these cells, in contrast to ASC or dermal fibroblasts, showed increased proliferation and migration. Taken together, these results indicate that on transplantation, keratinocytes are primarily activated to promote wound closure. In contrast, dermal fibroblasts and, in particular, ASC respond vigorously to factors present in the wound bed, leading to increased secretion of angiogenesis/granulation tissue formation factors. Our findings have implications for the choice of cell type (ASC or dermal fibroblast) to be used in regenerative medicine strategies and indicate the importance of taking into account interactions with the wound bed when developing advanced therapies for difficult-to-close cutaneous wounds.