Successful Transplantation of Murine Hearts Preserved 24h Under Subzero Ischemia Using Novel Bio-Inspired Next Generation Cryoprotectants
1Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA), Johns Hopkins University School of Medicine, Baltimore, MD, 2X-Therma Inc., Richmond, CA
Meeting: 2020 American Transplant Congress
Abstract number: D-216
Keywords: Heart preservation, Ischemia, Preservation solutions, Waiting lists
Session Information
Session Name: Poster Session D: Non-Organ Specific: Organ Preservation/Ischemia Reperfusion Injury
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Extension of the organ ischemia window is of paramount importance to prolong viability of transplantable organs and to improve overall outcomes. Transport using a subzero temperature could be promising, but requires toxic cryoprotectant. We developed a novel class of bioinspired non-toxic cryoprotectants and here demonstrate first in vivo evidence to significantly extend subzero organ preservation to 24h in a murine heart transplant model.
*Methods: Heterotopic heart transplantation was performed in a syngeneic donor/recipient combination using male C57BL/6 mice. Three groups were studied (no ischemia, baseline control; hearts stored 24h at -5°C using new cryoprotectants, experimental group; hearts stored 24h in HTK at 4°C, control group). Static storage was performed without machine perfusion or oxygenation. Post-transplant functional graft assessment was assessed by daily palpation. Graft viability and tissue integrity was assessed by histology, immunohistochemistry, and gene expression (TNF-a, iNOS, IL-1 B, nrf-2, HO-1) at POD3 and POD30.
*Results: All experimental group heart grafts regained a regular heartbeat and sinus rhythm with survival through the study endpoint at POD30. Control group grafts did not regain any heartbeat. At POD3, mild cellular infiltration and ventricular inflammation was observed in the experimental and baseline groups with no statistical difference. The control group had severe infiltration/inflammation and myocyte degeneration. Intragraft inflammation and fibrosis showed a clear tendency to recover at POD30 in grafts of the experimental group as compared to control group. Relative expression of proinflammatory cytokines TNF-a and IL-1 in hearts of the experimental group was significantly lower as compared to the control group at POD3. Similarly, iNOS and nrf2 gene expression were relatively lower nor were alterations seen in the nrf2/HO-1 pathway in the experimental group vs. those stored in HTK.
*Conclusions: Novel cryoprotectants that prevent ice damage at subzero temperature have enabled successful preservation and transplantation of murine heart grafts well beyond the critical ischemia time for conventional static cold storage. Further exploration of the impact of subzero organ preservation on graft viability is ongoing.
To cite this abstract in AMA style:
Oh B, Callegari A, Kline M, Childs A, Lozano MIglesias, Brandacher G, Wei X. Successful Transplantation of Murine Hearts Preserved 24h Under Subzero Ischemia Using Novel Bio-Inspired Next Generation Cryoprotectants [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/successful-transplantation-of-murine-hearts-preserved-24h-under-subzero-ischemia-using-novel-bio-inspired-next-generation-cryoprotectants/. Accessed May 16, 2025.« Back to 2020 American Transplant Congress