Anti-CD47 monoclonal antibody therapy reduces ischemia-reperfusion injury of renal allografts in a porcine model of donation after cardiac death

Min Xu, Xuanchuan Wang, Babak Banan, Danielle L. Chirumbole, Sandra Garcia-Aroz, Aparna Balakrishnan, Deepak K. Nayak, Zhengyan Zhang, Jianluo Jia, Gundumi A. Upadhya, Joseph P. Gaut, Ronald Hiebsch, Pamela T. Manning, Ningying Wu, Yiing Lin, William C. Chapman

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

We investigated whether blockade of the CD47 signaling pathway could reduce ischemia-reperfusion injury (IRI) of renal allografts donated after cardiac death (DCD) in a porcine animal model of transplantation. Renal allografts were subjected to 30 minutes of warm ischemia, 3.5 hours of cold ischemia, and then perfused with a humanized anti-CD47 monoclonal antibody (CD47mAb) in the treatment group or HTK solution in the control group (n = 4/group). The animals were euthanized five days after transplantation. At the time of reperfusion, indocyanine green-based in vivo imaging showed that CD47mAb-treated organs had greater and more uniform reperfusion. On post-transplant days 3-5, the treatment group had lower values compared to the control for creatinine and blood urea nitrogen. Histological examination of allograft tissues showed a significant decrease of acute tubular injury in the CD47mAb-treated group compared to control. Compared to the control group, CD47mAb treatment significantly decreased genes expression related to oxidative stress (sod-1, gpx-1, and txn), the inflammatory response (il-2, il-6, inf-g, and tgf-b), as well as reduced protein levels of BAX, Caspase-3, MMP2, and MMP9. These data demonstrate that CD47mAb blockade decreases IRI and subsequent tissue injury in DCD renal allografts in a large animal transplant model.

Original languageEnglish
Pages (from-to)855-867
Number of pages13
JournalAmerican Journal of Transplantation
Volume18
Issue number4
DOIs
StatePublished - Apr 2018

Keywords

  • basic (laboratory) research/science
  • donors and donation: deceased
  • kidney (allograft) function/dysfunction
  • kidney transplantation/nephrology
  • translational research/science

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