Evidence map›Paper›PMID 41870150›Full record

ArticleXenotransplantation

Expression of Human Thrombomodulin Prevents Early Thrombocytopenia and Thrombotic Microangiopathy in Pig-to-Nonhuman Primate Orthotopic Liver Xenotransplantation.

Zhongqiang Zhang, Ting Li, Qiang Li, Bin Xie, Xinger Zhao, Jianbin Wang, Yaxun Huang, Jing Luo, Shali Wen, Yinchun Zhou and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Xenotransplantation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Zhongqiang ZhangDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Ting LiDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.ORCID https://orcid.org/0000-0002-9366-7116
Qiang LiDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Bin XieDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Xinger ZhaoDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Jianbin WangDepartment of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Yaxun HuangDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Jing LuoDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Shali WenDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Yinchun ZhouOperation Room, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Yong DengOperation Room, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Yanfang LuDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Yanyan JiangXenotransplantation and Regeneration Key Laboratory of Sichuan Province, Chengdu ClonOrgan Biotechnology Co. Ltd, Chengdu, China.
Jiequn LiDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.ORCID https://orcid.org/0000-0002-5285-2403
David K C CooperCenter For Transplantation Sciences, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0002-8899-9431
Dengke PanXenotransplantation and Regeneration Key Laboratory of Sichuan Province, Chengdu ClonOrgan Biotechnology Co. Ltd, Chengdu, China.ORCID https://orcid.org/0000-0002-7994-1465
Zhongzhou SiDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Haizhi QiDepartment of Liver Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Funding

Excellent Youth Foundation of Hunan Provincial Natural Science Foundation 2022JJ20087Joint Fund of the National Natural Science Foundation U24A20656Key R&D Program of Hunan Province 2022DK2002Key R&D Program of Hunan Province 2024DK2005National Key R&D Program of China 2024YFC3406800Scientific Research Project of Hunan Provincial Health Commission 202214023205
6 · The paper itself

Abstract

backgroundSevere thrombocytopenia and coagulation dysregulation remain major barriers to survival in pig-to-primate liver xenotransplantation models.

methodsPorcine livers with five genetic modifications (GTKO, CMAHKO, β4GalNT2KO, hCD55, and hTBM) were orthotopically transplanted into four Tibetan macaques under two conventional immunosuppressive protocols. Longitudinal monitoring included graft and multi-organ function, hematology, coagulation, and immune responses. Histopathological and immunohistochemical analyses were performed to characterize graft and recipient pathology.

resultsHigh expression of human thrombomodulin (hTBM) in donor livers effectively prevented early rapid and severe thrombocytopenia, with three of four recipients maintaining platelets >100 × 10

conclusionsGTKO/CMAHKO/β4GalNT2KO/hCD55/hTBM donor liver transplantation was associated with an absence of early severe thrombocytopenia, transfusion requirement, and TMA, but long-term survival was limited by immune-mediated rejection and cross-species incompatibilities in coagulation factor synthesis. Optimizing (i) donor genetic modifications and (ii) immunosuppressive therapy, with (iii) replacement of targeted coagulation factors will be crucial for achieving durable survival in pig liver xenotransplantation.

Indexed as

Liver TransplantationThrombocytopeniaThrombomodulinThrombotic MicroangiopathiesTransplantation, HeterologousAnimalsGraft RejectionGraft SurvivalHeterograftsHumansLiverMacacaSwineTHBD protein, humanThrombomodulinliverpigrejectionthrombocytopeniathrombotic microangiopathyTibetan macaquexenotransplantation

Identifiers

PMID41870150
PMCPMC13051420

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.