Serum Stabilized Naked Caspase-3 siRNA Protects Transplant Kidneys in a Porcine Auto-Transplantation Model
University of Leicester, University Hospitals of Leicester, Leicester, United Kingdom
Zhongshan Hospital, Fudan University, Shanghai, China
Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
Affiliated Hospital of Nantong University, Nantong, China
Meeting: 2013 American Transplant Congress
Abstract number: D1556
Background: Caspase-3 associated with apoptosis and inflammation plays a key role in ischemia reperfusion injury. The naked caspase-3 siRNA was effective in the cold preservation and ex vivo hemoreperfusion of the kidney, but its in vivo effects need to be further evaluated. Hence, a novel version of naked caspase-3 siRNA with super serum stability was applied in a porcine kidney auto-transplantation model.
Materials and Methods: The left kidney was retrieved from mini pigs and infused by University of Wisconsin solution with/without 0.3 mg caspase-3/negative siRNA (Ambion® In vivo siRNAs, n = 5) into the renal artery with the renal artery and vein clamped for 24-h cold storage (CS). After the right nephrectomy, the left kidney was auto-transplanted into the right for 2 weeks with an i.v. of 0.9 mg siRNA 1-h before reperfusion. The work was performed under the regulation layout by Chinese animal welfare authority.
Results: The expression of caspase-3 mRNA was reduced in both the post-CS and post-transplant kidneys preserved by caspase-3 siRNA, while the caspase-3 precursor was reduced in the post-CS kidneys and 17 kD active subunit was inhibited in the post-transplant kidneys respectively. The level of IL-1Β mRNA, apoptotic cells and myeloperoxidase+ cells, was all decreased in the post-CS and post-transplant kidneys. In addition, HMGB-1 was decreased only in the post-transplant kidneys, but no significant changes were revealed in TLR-3 and TLR-7 between the groups. Moreover, renal tissue damage was ameliorated by the siRNA, with better renal function.
Conclusion: The serum stabilized naked caspase-3 siRNA administered locally and systemically protected transplant kidneys via altering apoptosis, inflammation and immunity responses. Using this novel siRNA in a large animal kidney auto-transplantation model for 2 weeks provides invaluable data for future human clinical trials.
To cite this abstract in AMA style:
Yang C, Zhao T, Zhao Z, Jia Y, Li L, Rong R, Xu M, Nicholson M, Zhu T, Yang B. Serum Stabilized Naked Caspase-3 siRNA Protects Transplant Kidneys in a Porcine Auto-Transplantation Model [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/serum-stabilized-naked-caspase-3-sirna-protects-transplant-kidneys-in-a-porcine-auto-transplantation-model/. Accessed November 23, 2024.« Back to 2013 American Transplant Congress