Mesenchymal Stem Cells Overexpressing C-X-C Chemokine Receptor Type 4 Improve Early Liver Regeneration of Small-for-Size Liver Grafts
Mesenchymal Stem Cells Overexpressing C-X-C Chemokine Receptor Type 4 Improve Early Liver Regeneration of Small-for-Size Liver Grafts
复制标题
过度表达 C-X-C 4 型趋化因子受体的间充质干细胞可改善小型肝移植物的早期肝脏再生
DOI：
10.1002/lt.23577
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发表时间：
2013-02-01
影响因子：
4.6
通讯作者：
Liu, Yingbin
中科院分区：
文献类型：
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作者：
Du, Zhiyong;Wei, Cuifeng;Liu, Yingbin
间充质干细胞（MSC）治疗可以防止肝实质细胞丢失，促进组织修复。然而，较差的MSC植入是细胞治疗有效性的主要障碍之一，因为培养扩增的MSC逐渐下调C-X-C趋化因子受体4（CXCR 4）表达，并失去其向基质细胞衍生因子1a（SDF 1a）浓度梯度迁移的能力。在这项研究中，我们研究了CXCR 4-MSC输注是否可以保护肝细胞并刺激50%缩小体积肝移植（RIVER）的再生。将接受50%RBIG的大鼠随机分为3组：磷酸盐缓冲溶液（PBS）组、绿色荧光蛋白（GFP）MSC组和CXCR 4-MSC组。大鼠接受ImL PBS，有或没有GFP-MSC或CXCR 4-MSC的再悬浮。观察移植后骨髓间充质干细胞分泌因子、移植物功能、肝细胞凋亡和增殖情况、骨髓间充质干细胞移植效果以及移植后GFP阳性骨髓间充质干细胞SDF 1、白蛋白（Alb）和细胞角蛋白18（CK 18）的表达。全身输注GFP-MSCs导致肝损伤生物标志物的释放减少和肝细胞凋亡; CXCR 4过表达没有进一步减少肝损伤。然而，CXCR 4过表达增强了MSC在肝移植物中的植入，改善了对肝细胞增殖的影响，从而提供了显著的1周生存益处。移植CXCR 4-MSCs后，移植物中SDF 1的表达升高。移植后168 h，移植的MSCs不表达Alb和CK 18等肝细胞标志物。CXCR 4过表达增强了MSC的动员和移植到小尺寸肝移植物中，其中这些细胞促进了残肝的早期再生，而不是通过直接分化，而是可能通过旁分泌机制。肝移植19：215-225，2013。(c)2012年AASLD。
Mesenchymal stem cell (MSC) therapy can prevent hepatic parenchymal cell loss and promote tissue repair. However, poor MSC engraftment is one of the primary barriers to the effectiveness of cell therapy because culture-expanded MSCs progressively down-regulate C-X-C chemokine receptor type 4 (CXCR4) expression and lose their ability to migrate toward a concentration gradient of stromal cellderived factor 1a (SDF1a). In this study, we investigated whether a CXCR4-MSC infusion could protect hepatocytes and stimulate regeneration in 50% reduced size liver transplantation (RSLT). Rats that underwent 50% RSLT were randomly divided into 3 groups: a phosphate-buffered solution group (PBS), a green fluorescent protein (GFP)MSC group, and a CXCR4-MSC group. Rats received 1 mL of PBS with or without a resuspension of GFP-MSCs or CXCR4-MSCs. The factors secreted by MSCs, the graft function, the apoptosis and proliferation of hepatocytes, the efficacy of MSC engraftment, and the expression of SDF1, albumin (Alb), and cytokeratin 18 (CK18) in engrafted GFP-positive MSCs were assessed. A systemic infusion of GFP-MSCs led to a reduction of the release of liver injury biomarkers and apoptosis of hepatocytes; CXCR4 overexpression did not further reduce the liver injury. However, CXCR4 overexpression enhanced MSC engraftment in liver grafts, improved the effect on the proliferation of hepatocytes, and thus provided a significant 1-week survival benefit. SDF1 expression in grafts was elevated after transplanted CXCR4-MSCs were recruited to the remnant liver. However, engrafted MSCs did not express the markers of hepatocytes, including Alb and CK18, in vivo 168 hours after transplantation. CXCR4 overexpression enhanced the mobilization and engraftment of MSCs into small-for-size liver grafts, in which these cells promoted the early regeneration of the remnant liver not by direct differentiation but perhaps by a paracrine mechanism. Liver Transpl 19:215-225, 2013. (c) 2012 AASLD.