Roles of macrophage migration inhibitory factor in cartilage tissue engineering
Roles of macrophage migration inhibitory factor in cartilage tissue engineering
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DOI：
10.1002/jcp.26036
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发表时间：
2018-02-01
影响因子：
5.6
通讯作者：
Hoshi, Kazuto
中科院分区：
文献类型：
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作者：
Fujihara, Yuko;Hikita, Atsuhiko;Hoshi, Kazuto
为了在再生医学中获得稳定的结果，了解和控制移植组织的免疫反应是非常重要的。在我们之前的研究中，组织工程化软骨移植小鼠的耳廓软骨细胞表达免疫因子，包括巨噬细胞移动抑制因子(MIF)。由于MIF具有多效性，在本研究中，我们探讨了MIF在软骨再生医学中的作用。我们用C57BL/6J小鼠耳廓软骨细胞、胶原凝胶和聚乳酸支架制成组织工程化软骨，并将构建的软骨移植到同种异体皮下。组织工程化软骨移植后2周，MIF在软骨区的定位明显，但在8周时不明显。RAW264与软骨细胞共培养可显著增加软骨细胞MIF的表达，提示组织工程软骨移植细胞可通过刺激周围巨噬细胞增强MIF的表达。在软骨细胞培养中加入MIF后，II型胶原的表达增加，提示MIF能促进软骨细胞的成熟。同时，含有野生型(Mif+/+)软骨细胞的结构的甲苯胺蓝染色显示，在2周时，与MIF-/-敲除(Mif-/-)结构相比，异染性增加。然而，这一趋势在8周时被逆转，这表明Mif+/+结构中最初增加的软骨成熟在8周时恶化。由于Mif+/+构建物在2周时含有更多iNOS阳性的炎性巨噬细胞，MIF可能会诱导M1巨噬细胞极化的环境，这最终可能会在长期内恶化组织工程软骨的成熟。
To obtain stable outcomes in regenerative medicine, understanding and controlling immunological responses in transplanted tissues are of great importance. In our previous study, auricular chondrocytes in tissue-engineered cartilage transplanted in mice were shown to express immunological factors, including macrophage migration inhibitory factor (MIF). Since MIF exerts pleiotropic functions, in this study, we examined the roles of MIF in cartilage regenerative medicine. We made tissue-engineered cartilage consisting of auricular chondrocytes of C57BL/6J mouse, atellocollagen gel and a PLLA scaffold, and transplanted the construct subcutaneously in a syngeneic manner. Localization of MIF was prominent in cartilage areas of tissue-engineered cartilage at 2 weeks after transplantation, though it became less apparent by 8 weeks. Co-culture with RAW264 significantly increased the expression of MIF in chondrocytes, suggesting that the transplanted chondrocytes in tissue-engineered cartilage could enhance the expression of MIF by stimulation of surrounding macrophages. When MIF was added in the culture of chondrocytes, the expression of type II collagen was increased, indicating that MIF could promote the maturation of chondrocytes. Meanwhile, toluidine blue staining of constructs containing wild type (Mif+/+) chondrocytes showed increased metachromasia compared to MIF-knockout (Mif-/-) constructs at 2 weeks. However, this tendency was reversed by 8 weeks, suggesting that the initial increase in cartilage maturation in Mif+/+ constructs deteriorated by 8 weeks. Since the Mif+/+ constructs included more iNOS-positive inflammatory macrophages at 2 weeks, MIF might induce an M1 macrophage-polarized environment, which may eventually worsen the maturation of tissue-engineered cartilage in the long term.