Circulating pig‐specific DNA as a novel biomarker for monitoring xenograft rejection
Circulating pig‐specific DNA as a novel biomarker for monitoring xenograft rejection
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循环猪特异性 DNA 作为监测异种移植排斥反应的新型生物标志物
DOI：
10.1111/xen.12522
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发表时间：
2019
影响因子：
3.9
通讯作者：
Lisha Mou
中科院分区：
文献类型：
--
作者：
Ming Zhou;Ying Lu;Chengjiang Zhao;Junfang Zhang;D. Cooper;Chongwei Xie;Zongpei Song;Hanchao Gao;Z. Qu;Shan Lin;Yangyang Deng;H. Hara;Yongqiang Zhan;Zhengda Jiang;Yifan Dai;Changyou Wu;Z. Cai;Lisha Mou
监测免疫排斥反应对于猪异种移植物的长期存活至关重要。循环DNA是器官损伤或治疗反应的一种有前途的非侵入性生物标志物。在本研究中，在异种移植排斥反应期间监测循环猪特异性DNA（cpsDNA）。通过计算机模拟分析选择cpsDNA的潜在靶标，并通过PCR证实所选引物的种属特异性。随后，使用体外补体依赖性细胞毒性（CDC）试验评价cpsDNA作为生物标志物。然后，通过猪到小鼠细胞移植的体内成像模型评估早期诊断和对雷帕霉素的反应。最后，在猪-猴动脉贴片移植模型中监测cpsDNA。结果表明：（a）建立了一种用于小鼠和非人灵长类动物模型的cpsDNA定量方法;（B）cpsDNA反映了体外CDC;（c）cpsDNA在体内反映了异种移植排斥反应，并与猪-小鼠细胞移植中的异种移植物损失相关;（d）给予雷帕霉素时，cpsDNA显著降低;（e）在猪-猴动脉贴片移植中可检测到动态cpsDNA。总之，cpsDNA的测量可以被证明是一种侵入性较小，但更特异和敏感的低成本生物标志物，能够监测异种移植排斥反应和对免疫抑制治疗的反应。
Monitoring for immune rejection is crucial for long‐term survival of pig xenografts. Circulating DNA is a promising non‐invasive biomarker for either organ injury or response to therapy. In this study, circulating pig‐specific DNA (cpsDNA) was monitored during xenograft rejection. Potential targets of cpsDNA were selected by in silico analysis, and species specificity of selected primers was confirmed by PCR. Subsequently, cpsDNA as a biomarker was evaluated using a complement‐dependent cytotoxicity (CDC) assay in vitro. Then, early diagnosis and response to rapamycin were assessed by an in vivo imaging model of pig‐to‐mouse cell transplantation. Finally, cpsDNA was monitored in a pig‐to‐monkey artery patch transplantation model. The results showed that (a) a method of cpsDNA quantitation was established for application in mouse and nonhuman primate models; (b) cpsDNA reflected CDC in vitro; (c) cpsDNA in vivo mirrored xenograft rejection, and correlated with xenograft loss in pig‐to‐mouse cell transplantation; (d) cpsDNA was significantly reduced when rapamycin was administered; and (e) dynamic cpsDNA was detectable in pig‐to‐monkey artery patch transplantation. In conclusion, measurement of cpsDNA could prove to be a less invasive, but more specific and sensitive low‐cost biomarker enabling monitoring of xenograft rejection and the response to immunosuppressive therapy.
影响因子：
56.9
作者：
C. Phelps;C. Koike;T. Vaught;J. Boone;K. Wells;Shu-Hung Chen;S. Ball;S. Specht;I. Polejaeva;Jeff A. Monahan;P. Jobst;Sugandha B. Sharma;Ashley E. Lamborn;A. S. Garst;M. Moore;A. Demetris;W. Rudert;R. Bottino;S. Bertera;M. Trucco;T. Starzl;Yifan Dai;D. Ayares
通讯作者：
C. Phelps;C. Koike;T. Vaught;J. Boone;K. Wells;Shu-Hung Chen;S. Ball;S. Specht;I. Polejaeva;Jeff A. Monahan;P. Jobst;Sugandha B. Sharma;Ashley E. Lamborn;A. S. Garst;M. Moore;A. Demetris;W. Rudert;R. Bottino;S. Bertera;M. Trucco;T. Starzl;Yifan Dai;D. Ayares
影响因子：
3.8
作者：
Williams CD;Antoine DJ;Shaw PJ;Benson C;Farhood A;Williams DP;Kanneganti TD;Park BK;Jaeschke H
通讯作者：
Jaeschke H
影响因子：
15.9
作者：
Imaeda, Avlin B.;Watanabe, Azuma;Mehall, Wajahat Z.
通讯作者：
Mehall, Wajahat Z.