Monoclonal Antibodies Cut Ischemia-Reperfusion Injury
WEDNESDAY, Nov. 22, 2017 -- Anti-CD47 monoclonal antibody (CD47mAb) therapy reduces ischemia-reperfusion injury of renal allografts in an animal transplantation model, according to a study published online Oct. 31 in the American Journal of Transplantation.
Min Xu, M.D., Ph.D., from the Washington University School of Medicine in St. Louis, and colleagues 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 and 3.5 hours of cold ischemia followed by perfusion with either a humanized CD47mAb (treatment group; n = 4) or Histidine-Tryptophan-Ketoglutarate solution (control group; n = 4).
Using in vivo imaging, the researchers found that CD47mAb-treated organs had greater and more uniform reperfusion. The treatment group had lower creatinine and blood urea nitrogen values on post-transplant days three to five compared with the control group. There was a significant decrease of acute tubular injury upon histological examination of allograft tissues in the CD47mAb-treated group versus controls. CD47mAb treatment also significantly decreased gene expression related to oxidative stress (sod-1, gpx-1, and txn) and the inflammatory response (il-2, il-6, inf-g, and tgf-b) and 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," conclude the authors.
Several authors disclosed financial ties to biopharmaceutical companies, including Tioma Therapeutics, which provided the monoclonal antibodies.
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Posted: November 2017