Spatiotemporal immune atlas of the first clinical-grade, gene-edited pig-to-human kidney xenotransplant.
العنوان: | Spatiotemporal immune atlas of the first clinical-grade, gene-edited pig-to-human kidney xenotransplant. |
---|---|
المؤلفون: | Cheung MD; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Asiimwe R; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Erman EN; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Fucile CF; Informatics Institute, University of Alabama at Birmingham; Birmingham, AL, USA., Liu S; Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham; Birmingham, AL, USA., Sun CW; Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham; Birmingham, AL, USA., Hanumanthu VS; Flow Cytometry & Single Cell Core Facility, University of Alabama at Birmingham; Birmingham, AL, USA., Pal HC; Flow Cytometry & Single Cell Core Facility, University of Alabama at Birmingham; Birmingham, AL, USA., Wright ED; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Ghajar-Rahimi G; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Epstein D; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Orandi BJ; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Kumar V; Department of Medicine, University of Alabama at Birmingham; Birmingham, AL, USA., Anderson DJ; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Greene ME; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Bell M; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Yates S; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Moore KH; Department of Medicine, University of Alabama at Birmingham; Birmingham, AL, USA., LaFontaine J; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Killian JT Jr; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Baker G; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Perry J; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Reed R; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Little SC; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Rosenberg AF; Informatics Institute, University of Alabama at Birmingham; Birmingham, AL, USA.; Department of Microbiology, University of Alabama at Birmingham; Birmingham, AL, USA., George JF; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Locke JE; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA., Porrett PM; Department of Surgery, University of Alabama at Birmingham; Birmingham, AL, USA. |
المصدر: | Research square [Res Sq] 2023 Jan 09. Date of Electronic Publication: 2023 Jan 09. |
نوع المنشور: | Preprint |
اللغة: | English |
بيانات الدورية: | Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE |
مستخلص: | Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages expressed genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft was detected. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation. Competing Interests: Competing Interests Statement The following authors receive or have received salary support from a research grant from United Therapeutics: RA, EDW, CFF, DE, BJO, MB, GB, JP, RR, SCL, AFR, JEL, and PMP. |
التعليقات: | Update in: Nat Commun. 2024 Apr 11;15(1):3140. (PMID: 38605083) |
معلومات مُعتمدة: | T32 AI007051 United States AI NIAID NIH HHS; T32 DK007545 United States DK NIDDK NIH HHS; T32 DK116672 United States DK NIDDK NIH HHS; T32 GM008361 United States GM NIGMS NIH HHS |
تواريخ الأحداث: | Date Created: 20230130 Latest Revision: 20240422 |
رمز التحديث: | 20240422 |
مُعرف محوري في PubMed: | PMC9882594 |
DOI: | 10.21203/rs.3.rs-2382345/v1 |
PMID: | 36711785 |
قاعدة البيانات: | MEDLINE |
كن أول من يترك تعليقا!