Immunological response to tissue-engineered cartilage derived from auricular chondrocytes and a PLLA scaffold in transgenic mice

Immunological response to tissue-engineered cartilage derived from auricular chondrocytes and a PLLA scaffold in transgenic mice
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DOI:
10.1016/j.biomaterials.2009.10.053
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发表时间:
2010-02-01
期刊:
影响因子:
14
通讯作者:
Hoshi, Kazuto
Hoshi, Kazuto
中科院分区:
工程技术1区
文献类型:
--
作者:
Fujihara, Yuko;Takato, Tsuyoshi;Hoshi, Kazuto

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在组织工程构建体中,对生物材料的免疫反应可能会潜在地恶化组织再生的结果,但在组织工程构建体中,宿主和供体之间的免疫反应仍有待澄清。在本研究中,我们将由C57BL/6小鼠耳廓软骨细胞和聚l -乳酸支架(MW:200,000)组成的组织工程软骨构建体同种移植到C57BL/6背景的EGFP转基因小鼠体内,并通过供体来源和宿主来源的细胞定位来评估其应答,后者以EGFP的存在来区分。当供体来源的细胞构成再生软骨区域时,宿主来源的细胞在最初两周内数量增加,然后减少并排除到非软骨区域。此外,EGFP阳性大多与F4/80共定位,这表明在组织工程构建物中,大多数宿主来源的细胞可能是巨噬细胞。组织工程软骨结构的免疫组化染色显示软骨细胞中免疫特权相关因子的表达。如巨噬细胞迁移抑制因子(MIF)、fas配体(FasL)等。体外培养软骨细胞和巨噬细胞可增加软骨细胞中MIF和FasL的表达,提示组织工程软骨构建中的软骨细胞可通过表达与免疫特权相关的因子来调节宿主源性巨噬细胞的行为。2009爱思唯尔有限公司版权所有。
The immune response against biomaterials in tissue-engineered constructs could potentially worsen the outcome of tissue regeneration, but immunological reactions between host and donor in tissue-engineered constructs remain to be clarified. In the present study, we syngenically transplanted tissue-engineered cartilage constructs consisting of C57BL/6 mice auricular chondrocytes and poly-L-lactic acid scaffolds (MW:200,000) into EGFP transgenic mice of C57BL/6 background, and evaluated the response by the localization of donor-derived and host-derived cells, the latter of which were distinguished by the presence of EGFP. While donor-derived cells constituted the areas of regenerated cartilage, host-derived cells were increased in number for the initial two weeks, and then decreased and excluded to non-cartilage areas thereafter. Furthermore, EGFP positivity was mostly co-localized with that of F4/80, suggesting most of the host-derived cells in the tissue-engineered constructs could be macrophages. Immunohistochemical staining of the tissue-engineered cartilage constructs revealed expression of factors related to immune privilege in chondrocytes. such as macrophage migration inhibitory factor (MIF), fas ligand (FasL) and others. Co-culture of chondrocytes and macrophages in vitro increased the expression of MIF and FasL in the chondrocytes, suggesting that chondrocytes in tissue-engineered cartilage constructs could regulate the actions of host-derived macrophages by expressing factors related to immune privilege. (C) 2009 Elsevier Ltd. All rights reserved.