Tissue regeneration using macrophage migration inhibitory factor-impregnated gelatin microbeads in cutaneous wounds.

Tissue regeneration using macrophage migration inhibitory factor-impregnated gelatin microbeads in cutaneous wounds.
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DOI:
10.1016/s0002-9440(10)61238-2
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发表时间:
2005-12
期刊:
The American journal of pathology
影响因子:
--
通讯作者:
Yunan Zhao;T. Shimizu;J. Nishihira†;Y. Koyama;T. Kushibiki;A. Honda;Hirokazu Watanabe;R. Abe;Y. Tabata;H. Shimizu
Yunan Zhao;T. Shimizu;J. Nishihira†;Y. Koyama;T. Kushibiki;A. Honda;Hirokazu Watanabe;R. Abe;Y. Tabata;H. Shimizu
中科院分区:
其他
文献类型:
--
作者:
Yunan Zhao;T. Shimizu;J. Nishihira†;Y. Koyama;T. Kushibiki;A. Honda;Hirokazu Watanabe;R. Abe;Y. Tabata;H. Shimizu

文献摘要

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迁移抑制因子(MIF)响应组织损伤,并调节炎症和免疫过程。为了阐明MIF在皮肤伤口愈合中的功能,我们分析了MIF敲除(KO)小鼠。从MIF KO和野生型(WT)小鼠的背部皮肤切除伤口后,与WT小鼠相比,MIF KO小鼠的愈合显著延迟。与MIF KO小鼠成纤维细胞相比,脂多糖处理显著增加WT小鼠成纤维细胞中的[3 H]胸苷摄取。此外,1-油酰-2-溶血磷脂酸处理后,在MIF KO小鼠中观察到成纤维细胞和角质形成细胞迁移显著减少。我们随后检查了MIF浸渍的明胶缓释微珠是否可以加速皮肤伤口愈合。与不使用微珠的单次MIF注射相比,在伤口边缘周围注射超过1.5 μg/500 μl的MIF浸渍的明胶微珠加速伤口愈合。MIF浸渍的明胶微珠也加速了C57 BL/6小鼠和糖尿病db/db小鼠的皮肤伤口愈合。此外,将MIF浸渍的明胶微珠掺入植入MIF KO小鼠的人工真皮中加速了前胶原的产生和毛细血管的形成。这些发现表明,MIF是至关重要的,在加速皮肤伤口愈合和MIF浸渍明胶微珠代表一个有前途的治疗,以促进皮肤伤口愈合。
Migration inhibitory factor (MIF) responds to tissue damage and regulates inflammatory and immunological processes. To elucidate the function of MIF in cutaneous wound healing, we analyzed MIF knockout (KO) mice. After the excision of wounds from the dorsal skin of MIF KO and wild-type (WT) mice, healing was significantly delayed in MIF KO mice compared to WT mice. Lipopolysaccharide treatment significantly increased [3H]thymidine uptake in WT mouse fibroblasts compared to MIF KO mouse fibroblasts. Furthermore, there was a significant reduction in fibroblast and keratinocyte migration observed in MIF KO mice after 1-oleoyl-2-lysophosphatidic acid treatment. We subsequently examined whether MIF-impregnated gelatin slow-release microbeads could accelerate skin wound healing. Injection of more than 1.5 μg/500 μl of MIF-impregnated gelatin microbeads around a wound edge accelerated wound healing compared to a single MIF injection without the use of microbeads. MIF-impregnated gelatin microbeads also accelerated skin wound healing in C57BL/6 mice and diabetic db/db mice. Furthermore, incorporating MIF-impregnated gelatin microbeads into an artificial dermis implanted into MIF KO mice accelerated procollagen production and capillary formation. These findings suggest that MIF is crucial in accelerating cutaneous wound healing and that MIF-impregnated gelatin microbeads represent a promising treatment to facilitate skin wound healing.