Treatment of Cutaneous Ulcers with Multilayered Mixed Sheets of Autologous Fibroblasts and Peripheral Blood Mononuclear Cells
Treatment of Cutaneous Ulcers with Multilayered Mixed Sheets of Autologous Fibroblasts and Peripheral Blood Mononuclear Cells
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DOI：
10.1159/000489767
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Hamano, Kimikazu
中科院分区：
文献类型：
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作者：
Mizoguchi, Takahiro;Ueno, Koji;Hamano, Kimikazu
背景/目标：我们开发了一种由自体成纤维细胞和外周血单核细胞组成的混合细胞片，其在小鼠和兔模型中具有高的血管生成和伤口愈合能力，可对抗难治性皮肤溃疡。为了提高混合片材的有效性，我们开发了多层混合片材。方法：我们评估了多层膜对小鼠皮肤溃疡的治疗作用。生长因子和趋化因子通过酶联免疫吸附试验进行评估。血管生成和成纤维细胞迁移通过使用管形成和迁移测定来测量。观察糖尿病小鼠皮肤溃疡愈合率。结果如下：分泌的血管内皮生长因子，肝细胞生长因子，转化生长因子，C-X-C基序趋化因子配体（CXCL）-1，CXCL-2的浓度在多层片材中远远高于单层混合细胞片材（单层片材）和单独成纤维细胞的多层片材（成纤维细胞片材）。在体外实验中，与单层和成纤维细胞片相比，多层片中的上清液增强了血管生成效力和成纤维细胞迁移。在愈合的早期阶段，多层片材处理组的伤口愈合率高于未处理组（对照组）。此外，与对照组中的组织相比，用多层片材处理的组织中的血管腔面积和微血管密度均显著增加。结论：多层膜通过提供生长因子和细胞因子促进皮肤创面愈合和微血管新生。因此，我们的数据表明，多层片材可能是一种有前途的治疗材料，难治性皮肤溃疡。(C)2018作者（S）由S发布。Karger AG，巴塞尔
Background/Aims: We have developed a mixed-cell sheet consisting of autologous fibroblasts and peripheral blood mononuclear cells with a high potency for angiogenesis and wound healing against refractory cutaneous ulcers in mouse and rabbit models. To increase the effectiveness of the mixed sheet, we developed a multilayered mixed sheet. Methods: We assessed the therapeutic effects of multilayered sheets on cutaneous ulcers in mice. Growth factors and chemokines were assessed by enzyme-linked immunosorbent assay. Angiogenesis and fibroblast migration were measured by using tube formation and migration assays. Wound healing rate of cutaneous ulcers was evaluated in mice with diabetes mellitus. Results: The concentration of secreted vascular endothelial growth factor, hepatocyte growth factor, transforming growth factor, C-X-C motif chemokine ligand (CXCL)-1, and CXCL-2 in multilayered sheets was much higher than that in single-layered mixed-cell sheets (singlelayered sheets) and multilayered sheets of fibroblasts alone (fibroblast sheets). The supernatant in multilayered sheets enhanced angiogenic potency and fibroblast migration compared with single-layered and fibroblast sheets in an in vitro experiment. The wound healing rate in the multilayered sheet-treated group was higher compared with the no-treatment group (control) at the early stage of healing. Moreover, both vessel lumen area and microvessel density in tissues treated with multilayered sheets were significantly increased compared with tissues in the control group. Conclusion: Multilayered sheets promoted wound healing and microvascular angiogenesis in the skin by supplying growth factors and cytokines. Accordingly, our data suggest that multilayered sheets may be a promising therapeutic material for refractory cutaneous ulcers. (C) 2018 The Author(s) Published by S. Karger AG, Basel