Evidence map›Paper›PMID 41956816›Full record

ArticleXenotransplantation

Donor-Derived Cell-Free DNA (dd-cfDNA) as an Early Noninvasive Biomarker of Graft Injury in Pig-to-Monkey Islet Xenotransplantation.

Ji-Jing Yan, Jong-Min Kim, Sang-Ik Cho, Hyori Kim, Kyungmin Kwak, Hyunil Kim, Eun-Jee Oh, Jaeseok Yang, Chung-Gyu Park, Jong Cheol Jeong and 1 more

Abstract read
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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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Future of xenotransplantation in Korea.Clinical transplantation and research · 2026
    Review
  2. 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

11 authors.

Ji-Jing YanDivision of Nephrology, Seoul National University Bundang Hospital, Seongnam, South Korea.ORCID https://orcid.org/0000-0002-4048-1406
Jong-Min KimDepartment of Animal Health and Welfare, College of Health and Medical Sciences, Cheongju University, Cheongju, South Korea.ORCID https://orcid.org/0000-0003-0906-0117
Sang-Ik ChoDepartment of Medical Sciences, Graduate School of The Catholic University, Seoul, South Korea.
Hyori KimAsan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
Kyungmin KwakOptipharm Inc., Cheongju, South Korea.ORCID https://orcid.org/0000-0002-7377-9743
Hyunil KimOptipharm Inc., Cheongju, South Korea.
Eun-Jee OhDepartment of Laboratory Medicine, Seoul St. Mary's Hospital, Research and Development Institute For In Vitro Diagnostic Medical Devices, College of Medicine, The Catholic University, Seoul, South Korea.
Jaeseok YangDivision of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Chung-Gyu ParkDepartment of Microbiology and Immunology, Department of Biomedical Sciences, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.ORCID https://orcid.org/0000-0003-4083-8791
Jong Cheol JeongDivision of Nephrology, Seoul National University Bundang Hospital, Seongnam, South Korea.ORCID https://orcid.org/0000-0003-0301-7644
Beom Seok KimDivision of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.ORCID https://orcid.org/0000-0002-5732-2583

Funding

Korea Health Industry Development Institute
6 · The paper itself

Abstract

backgroundIn pig-to-nonhuman primate islet transplantation, reliable, sensitive biomarkers are needed to detect graft damage at an early stage before irreversible islet loss occurs. In our study, we investigated donor-derived cell-free DNA (dd-cfDNA) as an early, noninvasive biomarker of graft injury by analyzing its correlation with porcine C-peptide levels, complement activation markers, and donor-specific antibodies (DSAs).

methodsStreptozotocin-induced diabetic cynomolgus monkeys received 50 000-100 000 IEQ/kg of intraportal islets from quadruple-knockout (QKO; GGTA1, CMAH, B4GALNT2, and A3GALT2) pigs. Cohort 1 received antithymocyte globulin (ATG), tacrolimus, mycophenolate mofetil (MMF), and anti-inflammatory agents (i.e., anakinra, adalimumab, and tocilizumab), whereas Cohort 2 received the same regimen plus rituximab and crovalimab. Graft function and immune responses were assessed by measuring porcine C-peptide levels, complement activation markers, histology, and dd-cfDNA kinetics.

resultsCohort 1 showed transient porcine C-peptide secretion with marked dd-cfDNA elevation at 7 d postoperatively that coincided with complement activation (i.e., C5a and membrane attack complex (MAC)) and dense CD3

conclusionsOur study revealed that dd-cfDNA levels correlate with graft damage and C5a in QKO porcine islet xenografts, which corroborates dd-cfDNA utility as an early biomarker for predicting instant blood-mediated inflammatory reaction (IBMIR). These findings indicate that dd-cfDNA may be able to detect early islet xenograft damage.

Indexed as

Cell-Free Nucleic AcidsGraft RejectionIslets of Langerhans TransplantationTransplantation, HeterologousAnimalsBiomarkersC-PeptideDiabetes Mellitus, ExperimentalGraft SurvivalHeterograftsMacaca fascicularisMaleSwineBiomarkersCell-Free Nucleic AcidsC-Peptidecomplement activationdonor‐derived cell‐free DNAislet xenotransplantationporcine c‐peptide

Identifiers

PMID41956816
PMCPMC13065465

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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.