Allman A J, McPherson T B, Badylak S F, Merrill L C, Kallakury B, Sheehan C, Raeder R H, Metzger D W
Center for Immunology and Microbial Disease, MC 151, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
Transplantation. 2001 Jun 15;71(11):1631-40. doi: 10.1097/00007890-200106150-00024.
Porcine small intestinal submucosa (SIS) is an acellular, naturally derived extracellular matrix (ECM) that has been used for tissue remodeling and repair in numerous xenotransplantations. Although a vigorous immune response to xenogeneic extracellular matrix biomaterials is expected, to date there has been evidence for only normal tissue regeneration without any accompanying rejection. The purpose of this study was to determine the reason for a lack of rejection.
Mice were implanted s.c. with xenogeneic tissue, syngeneic tissue, or SIS, and the graft site analyzed histologically for rejection or acceptance. Additionally, graft site cytokine levels were determined by reverse transcriptase polymerase chain reaction and SIS-specific serum antibody isotype levels were determined by ELISA.
Xenogeneically implanted mice showed an acute inflammatory response followed by chronic inflammation and ultimately graft necrosis, consistent with rejection. Syngeneically or SIS implanted mice, however, showed an acute inflammatory response that diminished such that the graft ultimately became indistinguishable from native tissue, observations that are consistent with graft acceptance. Graft site cytokine analysis showed an increase in interleukin-4 and an absence of interferon-gamma. In addition, mice implanted with SIS produced a SIS-specific antibody response that was restricted to the IgG1 isotype. Reimplantation of SIS into mice led to a secondary anti-SIS antibody response that was still restricted to IgG1. Similar results were observed with porcine submucosa derived from urinary bladder. To determine if the observed immune responses were T cell dependent, T cell KO mice were implanted with SIS. These mice expressed neither interleukin-4 at the implant site nor anti-SIS-specific serum antibodies but they did accept the SIS graft.
Porcine extracellular matrix elicits an immune response that is predominately Th2-like, consistent with a remodeling reaction rather than rejection.
猪小肠黏膜下层（SIS）是一种无细胞的、天然来源的细胞外基质（ECM），已被用于众多异种移植中的组织重塑和修复。尽管预计会对异种细胞外基质生物材料产生强烈的免疫反应，但迄今为止，仅有正常组织再生的证据，而无任何伴随的排斥反应。本研究的目的是确定缺乏排斥反应的原因。
将异种组织、同基因组织或SIS皮下植入小鼠体内，并对移植部位进行组织学分析以确定排斥或接受情况。此外，通过逆转录聚合酶链反应测定移植部位细胞因子水平，并通过酶联免疫吸附测定法测定SIS特异性血清抗体亚型水平。
异种植入的小鼠表现出急性炎症反应，随后是慢性炎症，最终移植组织坏死，这与排斥反应一致。然而，同基因或SIS植入的小鼠表现出急性炎症反应，炎症反应逐渐减轻，最终移植组织与天然组织难以区分，这些观察结果与移植接受情况一致。移植部位细胞因子分析显示白细胞介素-4增加，而干扰素-γ缺乏。此外，植入SIS的小鼠产生了SIS特异性抗体反应，该反应仅限于IgG1亚型。将SIS再次植入小鼠导致二次抗SIS抗体反应，该反应仍仅限于IgG1。从膀胱来源的猪黏膜下层观察到类似结果。为了确定观察到的免疫反应是否依赖于T细胞，将SIS植入T细胞敲除小鼠体内。这些小鼠在植入部位既不表达白细胞介素-4，也不产生抗SIS特异性血清抗体，但它们确实接受了SIS移植。
猪细胞外基质引发的免疫反应主要类似于Th2，这与重塑反应而非排斥反应一致。
