Evidence map›Paper›PMID 31293016›Full record

ArticleXenotransplantation2019

Preparation of hybrid porcine thymus containing non-human primate thymic epithelial cells in miniature swine.

Mitsuhiro Sekijima, Hisashi Sahara, Akira Shimizu, Takehiro Iwanaga, Takahiro Murokawa, Yuichi Ariyoshi, Thomas Pomposelli, Mohsen Khosravi Maharlooei, Megan Sykes, Kazuhiko Yamada

Open access · greenAbstract read
In one paragraph

Article in Xenotransplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 29% of its field
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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Developments in kidney xenotransplantation.Frontiers in immunology · 2023
    Review
  2. Progress towards xenogenic tolerance.Current opinion in organ transplantation · 2020
    Review
  3. Article
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

10 authors at 3 institutions in 2 countries.

Mitsuhiro SekijimaDivision of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan.
Hisashi SaharaDivision of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan.
Akira ShimizuDepartment of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
Takehiro IwanagaDivision of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan.
Takahiro MurokawaDivision of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan.
Yuichi AriyoshiDivision of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan.
Thomas PomposelliDepartment of Surgery, Columbia University Center for Translational Immunology, Columbia University, New York, New York.
Mohsen Khosravi MaharlooeiDepartment of Surgery, Columbia University Center for Translational Immunology, Columbia University, New York, New York.
Megan SykesDepartment of Surgery, Columbia University Center for Translational Immunology, Columbia University, New York, New York.
Kazuhiko YamadaDepartment of Surgery, Columbia University Center for Translational Immunology, Columbia University, New York, New York.ORCID 0000-0002-0510-5843
Kagoshima University · JPColumbia University Irving Medical Center · USNippon Medical School · JP

Funding

XENOGRAFT TOLERANCE THROUGH MIXED CHIMERISMP01AI045897 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Megan Sykes · 2000 to 2026
$71.9M
Kagoshima University Research Awards NIAID P01AI045897National Institute of Allergy and Infectious DiseasesNIAID NIH HHS P01 AI045897
6 · The paper itself

Abstract

backgroundWe have achieved greater than a 6-month survival of a life-supporting kidney co-transplanted with a vascularized thymic graft into non-human primates (NHPs). Although we have achieved pig-specific unresponsiveness in vitro, immunosuppression was not able to be fully weaned. Studies in mice and humanized mice suggest that a hybrid pig thymus (Hyb-thy)-containing host thymic epithelial cells (TECs) can optimize intra-thymic selection, achieving xenograft tolerance with improved reconstitution of T-cell function.

methodsWe have tested the feasibility of the preparation of a Hyb-thy that contains NHP TECs in the donor thymic grafts. We first prepared the Hyb-thy in the donor pigs 2-3 weeks before xeno-Tx. We performed six cases of Hyb-thy preparation in six juvenile miniature swine. Two pigs received non-manipulated cynomolgus monkey thymic cells that were isolated from an excised atrophic thymus via injection into their thymic lobes (Group 1). The remaining four received thymic cells that were isolated from non-atrophic thymic glands (Groups 2 and 3). Pigs in Group 2 received unmanipulated thymic cells in one thymic lobe, as well as CD2-positive cell-depleted TEC-enriched cells in the contralateral lobe. Pigs in Group 3 received TEC-enriched cells alone.

resultsAll thymus-injected pigs received tacrolimus and rapamycin until endpoint (POD16). We detected cynomolgus monkey TEC networks in pig thymus from Groups 1 and 3, while pigs in Group 2 rejected the thymic cells. We demonstrated the preparation of Hyb-thy in pigs using tacrolimus plus rapamycin therapy.

conclusionsOur results suggest that the enrichment of TEC from the excised NHP thymus facilitated NHP TEC engraftment in pig thymus.

Indexed as

AnimalsEpithelial CellsGraft RejectionGraft SurvivalImmune ToleranceImmunosuppression TherapyMacaca fascicularisPrimatesSwineSwine, MiniatureThymus GlandTransplantation, Heterologoushybrid thymusnon-human primatepigvascularized thymusxenotransplantation

Identifiers

PMID31293016
PMCPMC6908759
OpenAlexW2960740816

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.