Host bone-marrow cells are a source of donor intimal smooth-muscle-like cells in murine aortic transplant arteriopathy
Host bone-marrow cells are a source of donor intimal smooth-muscle-like cells in murine aortic transplant arteriopathy
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DOI：
10.1038/89121
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发表时间：
2001-06-01
期刊：
影响因子：
82.9
通讯作者：
Mitchell, RN
中科院分区：
文献类型：
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作者：
Shimizu, K;Sugiyama, S;Mitchell, RN
长期的同种异体实体器官移植通常会出现弥漫性动脉内膜病变(移植物动脉疾病；GAD)，由平滑肌细胞(SMC)、细胞外基质和单个核细胞组成。GAD最终导致血管狭窄和缺血性移植物失败。虽然确切的机制尚不清楚，但慢性低水平的同种异体反应可能会诱导炎性细胞和/或功能障碍的血管壁细胞分泌生长因子，促进SMC的内膜募集、增殖和基质合成(1-3)。虽然先前的工作表明，同种异体心脏移植物GAD损伤的内皮和中膜SMC是供者来源的，但不能确定内膜SMC的来源。它们通常被认为来自供体介质(5)，导致以供体中层SMC增殖为目标的干预措施，但效果有限(6，7)。然而，其他报道表明，同种异体血管可能含有宿主来源的内皮和SMC(参考文献)。8，9)。此外，骨髓和循环细胞亚群可以分化为内皮细胞(10，11)，植入的人造血管移植物由宿主SMCs和内皮细胞种植(12，13)。在这里，我们使用小鼠主动脉移植来正式确定GAD病变中SMC的来源。β-半乳糖苷酶转基因受体的同种异体移植显示，血管内膜SMC几乎完全来自宿主细胞。将表达β-半乳糖苷酶的细胞移植到同种异体主动脉移植受者的骨髓中表明，内膜细胞包括骨髓来源的细胞。因此，GAD病变中的平滑肌样细胞可能来源于循环中的骨髓来源的前体细胞。
Long-term solid-organ allografts typically develop diffuse arterial intimal lesions (graft arterial disease; GAD), consisting of smooth-muscle cells (SMC), extracellular matrix and admired mononuclear leukocytes. GAD eventually culminates in vascular stenosis and ischemic graft failure. Although the exact mechanisms are unknown, chronic low-level alloresponses likely induce inflammatory cells and/or dysfunctional vascular wall cells to secrete growth factors that promote SMC intimal recruitment, proliferation and matrix synthesis(1-3). Although prior work demonstrated that the endothelium and medial SMCs lining GAD lesions in cardiac allografts are donor-derived, the intimal SMC origin could not be determined(4). They are generally presumed to originate from the donor media(5), leading to interventions that target donor medial SMC proliferation, with limited efficacy(6,7). However, other reports indicate that allograft vessels may contain host-derived endothelium and SMCs (refs. 8,9). Moreover, subpopulations of bone-marrow and circulating cells can differentiate into endothelium(10,11), and implanted synthetic vascular grafts are seeded by host SMCs and endothelium(12,13). Here we used murine aortic transplants to formally identify the source of SMCs in GAD lesions. Allografts in beta -galactosidase transgenic recipients showed that intimal SMCs derived almost exclusively from host cells. Bone-marrow transplantation of beta -galactosidase-expressing cells into aortic allograft recipients demonstrated that intimal cells included those of marrow origin. Thus, smooth-muscle-like cells in GAD lesions can originate from circulating bone-marrow-derived precursors.