Successful Long Term Survival of Vascularized Composite Allografts After Extended Preservation at Subzero Temperatures Using Bioinspired Next Generation Cryoprotectants
1X-Therma Inc., Richmond, CA, 2Johns Hopkins University School of Medicine, Baltimore, MD, 3Erasmus MC, Rotterdam, Netherlands
Meeting: 2021 American Transplant Congress
Abstract number: 381
Keywords: Ischemia, Perfusion solutions, Preservation
Topic: Clinical Science » Organ Inclusive » Non-Organ Specific:Organ Preservation/Ischemia Reperfusion Injury
Session Information
Session Name: Surgical Issues and Deceased Donor Management
Session Type: Rapid Fire Oral Abstract
Date: Tuesday, June 8, 2021
Session Time: 6:00pm-7:00pm
Presentation Time: 6:35pm-6:40pm
Location: Virtual
*Purpose: Vascularized composite allotransplantation (VCA) is a viable reconstructive option for patients with devastating tissue defects. However, the field is constrained by short tolerable ischemia times. Extending tolerated ischemia time to days instead of hours would be transformative for VCA with regard to organ matching and exchange as well as allow for innovative protocols for recipient conditioning. We here present first outcomes using a novel organ preservation solution containing peptoids (XT-ViVo) for extended preservation of rat penile grafts for up to 72 hours in a syngeneic transplant model.
*Methods: Lewis rats served as donors and recipients of heterotopic penile transplants. Grafts were flushed with heparinized saline and then directly transplanted (control, N=6) or perfused with either 5mL of HTK (control, N=18, stored at 4oC) or 5mL of XT-ViVo (intervention, N=24, stored at -5oC). HTK and XT-ViVo perfused grafts were preserved for 24, 48, or 72 hours prior to transplantation. Grafts were clinically monitored daily until study endpoints of POD3 and 30 and then assessed by histology (H&E) and by IHC (Caspase-3). RNA sequencing was performed to analyze inflammatory gene expression.
*Results: All grafts with minimal ischemia showed no signs of clinical necrosis at POD3 or POD30. HTK preserved grafts all experienced distal necrosis at POD3 after preservation for 24, 48 or 72 hours. 5/6 of HTK grafts preserved for 72 hours were fully necrotic by POD30. In contrast, 24h and 48h XT-ViVo perfused grafts had excellent clinical outcomes at POD30; some epidermolysis was present in the grafts in the days before POD7, which subsequently resolved. 4/6 of 72h XT-ViVo perfused grafts showed distal necrosis at POD30 and 2/6 experienced only minimal distal epidermolysis and appeared clinically normal at POD30. In 48/72h distal tissue samples XT-ViVo grafts showed moderate inflammation and minimal necrosis, HTK grafts severe inflammation and major necrosis
*Conclusions: We report the first VCA survival after 48-72 hours of preservation at subzero temperature with a peptoid-based cryoprotective solution
To cite this abstract in AMA style:
Kline M, Fidder S, Callegari A, Matoso A, Oh B, Lombardo K, Etra J, Vasilic D, Childs A, Redett R, Brandacher G, Wei X. Successful Long Term Survival of Vascularized Composite Allografts After Extended Preservation at Subzero Temperatures Using Bioinspired Next Generation Cryoprotectants [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/successful-long-term-survival-of-vascularized-composite-allografts-after-extended-preservation-at-subzero-temperatures-using-bioinspired-next-generation-cryoprotectants/. Accessed November 21, 2024.« Back to 2021 American Transplant Congress