Macrophage Participation in the Degradation and Remodeling of Extracellular Matrix Scaffolds

Macrophage Participation in the Degradation and Remodeling of Extracellular Matrix Scaffolds
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DOI:
10.1089/ten.tea.2008.0419
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发表时间:
2009-07-01
影响因子:
4.1
通讯作者:
Badylak, Stephen F.
Badylak, Stephen F.
中科院分区:
医学3区
文献类型:
--
作者:
Valentin, Jolene E.;Stewart-Akers, Ann M.;Badylak, Stephen F.

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由细胞外基质(ECM)组成的生物支架在临床前动物研究和人类临床应用中被广泛用于促进各种组织的重建和重建。这种支架影响宿主组织反应的机制只被部分了解,但单核巨噬细胞群发挥核心作用是合乎逻辑的。本研究评估了来自外周血的巨噬细胞在ECM支架降解中的作用。利用已建立的大鼠体壁重建模型,评价了碳二亚胺(CDI)-交联型支架材料对猪小肠黏膜下层(SIS)、非交联型SIS和自体体壁的降解作用。为了评估循环中巨噬细胞在降解过程中的作用,对每个支架的降解进行了评估,包括是否有因给予含氯屈膦酸盐脂质体而导致的巨噬细胞耗竭。结果表明,SIS支架和自体体壁的早期和快速降解都需要外周血单核细胞,CDI交联的SIS对巨噬细胞介导的降解具有抵抗力。
Biologic scaffolds composed of extracellular matrix (ECM) are widely used to facilitate remodeling and reconstruction of a variety of tissues in both preclinical animal studies and human clinical applications. The mechanisms by which such scaffolds influence the host tissue response are only partially understood, but it is logical that the mononuclear macrophage cell population plays a central role. The present study evaluated the role of macrophages that derive from peripheral blood in the degradation of ECM scaffolds. An established rat body wall reconstruction model was used to evaluate the degradation of carbodiimide (CDI)-crosslinked scaffolds composed of porcine small intestinal submucosa (SIS), noncrosslinked SIS, and autologous body wall. To assess the role of circulating macrophages in the degradation process, the degradation of each scaffold was assessed with and without macrophage depletion caused by administration of clodronate-containing liposomes. Results showed that peripheral blood monocytes are required for the early and rapid degradation of both SIS scaffolds and autologous body wall, and that CDI crosslinked SIS is resistant to macrophage-mediated degradation.