Recruitment of host progenitor cells in rat liver transplants.
Recruitment of host progenitor cells in rat liver transplants.
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DOI：
10.1002/hep.22653
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Williams GM
中科院分区：
文献类型：
--
作者：
Sun Z;Zhang X;Locke JE;Zheng Q;Tachibana S;Diehl AM;Williams GM
尽管MHC不相容，刘易斯DA大鼠肝移植无限期生存无免疫抑制，我们报告的研究寻求的机制负责。一年后，大部分肝脏对宿主抗DA抗体呈阳性反应。当移植小（50%）移植物时，招募更快，因为大多数器官在3个月时呈现宿主表型。原位杂交和PCR均检测到移植肝细胞中的Y染色体。此外，来自携带强GFP标记的转基因刘易斯大鼠的肝脏在移植到DA、GFP−宿主后随着时间的推移而失去标记。在同系XX至XY肝移植物中或在刘易斯XX至DA XY同种异体肝移植物中用环孢素A（CsA）10 mg/kg/d处理时，很少有肝细胞含有Y染色体。该剂量也在10天内阻止了肝脏的扩大。使用GFP+ XX刘易斯供体移植到GFP− XY DA宿主，我们在10天时在GFP+细胞中发现很少的Y DNA。在3-10天时存在宿主来源的OV-6和c-kit阳性、白蛋白阳性细胞，但具有CD 34标记物的细胞不太常见，并且一些细胞在10天时仍明显具有供体表型。CXCR-4阳性细胞随移植时间延长而增加，移植后1个月时已大量表达。我们得出结论：1.肝外细胞可分化为肝组织; 2.再生刺激加速干细胞募集; 3. CsA免疫抑制阻碍了再生和募集，以及4.供体GFP阳性细胞在移植后几乎不含宿主Y染色体，这表明细胞融合是不常见的，因此不太可能是导致我们观察到的基因型和表型变化的机制。
Despite MHC incompatibility, Lewis to DA rat liver transplants survive indefinitely without immunosuppression, and the studies we report sought the mechanism(s) responsible for this. At one year most of the liver reacted positively to host anti-DA antibody. When small (50%) grafts were transplanted, recruitment was more rapid as most of the organ assumed the host phenotype at 3 months. After transplantation the Y-chromosome was detected in the hepatocytes of XX to XY grafts by both in-situ hybridization and PCR. Further, livers from transgenic Lewis rats carrying strong GFP markers lost the marker with time after transplantation to DA, GFP− hosts. Few liver cells contained the Y chromosome in syngeneic XX to XY liver grafts or when the hosts of Lewis XX to DA XY allografts were treated with cyclosporine A (CsA) 10mgs/kg/day. This dosage also impeded enlargement of the liver at ten days. Using GFP+ XX Lewis donors transplanted to GFP− XY DA hosts, we found little Y DNA in GFP+ cells at 10 days. Host derived OV-6 and c-kit positive, albumen positive cells were present at 3-10 days, but cells with the CD34 marker were less common and some clearly still had the donor phenotype at ten days. CXCR-4 positive cells increased with time and were abundant at 1 month after transplantation. We conclude: 1. extra-hepatic cells can differentiate into liver tissues; 2. regenerative stimuli accelerate stem cell recruitment; 3. both regeneration and recruitment are impeded by CsA immunosuppression, and 4. donor GFP positive cells contained little host Y-chromosome after transplantation suggesting that cell fusion was uncommon and, therefore, unlikely to be the mechanism leading to the changes in genotype and phenotype we observed.
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影响因子：
64.8
作者：
Wang, X;Willenbring, H;Grompe, M
通讯作者：
Grompe, M
DOI：
10.1152/ajpgi.00314.2003
发表时间：
2004-09-01
影响因子：
4.5
作者：
Uchikura, K;Wada, T;Sun, ZL
通讯作者：
Sun, ZL
影响因子：
4.6
作者：
ten Hove, WR;van Hoek, B;Lagaaij, EL
通讯作者：
Lagaaij, EL
影响因子：
82.9
作者：
Willenbring, H;Bailey, AS;Grompe, M
通讯作者：
Grompe, M
影响因子：
64.8
作者：
Vassilopoulos, G;Wang, PR;Russell, DW
通讯作者：
Russell, DW