Original CommunicationDecrease in donor heart injury by recombinant clusterin protein in cold preservation with University of Wisconsin solution
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Animals and cell culture
C57BL/6j (B6) mice (males, 8–10 weeks old) were purchased from Jackson Laboratory (Bar Harbor, ME). All animal use procedures in this study were performed and monitored in accordance with the Canadian Council on Animal Care guideline under the protocols approved by the Animal Use Subcommittee at the University of British Columbia.
Primary human umbilical vein endothelial cells (HUVECs) were purchased from Lonza Walkersville (Walkersville, MD) and were immortalized with origin-deficient SV40 DNA
Preventing cell membrane disruption or necrosis in cultured HUVECs at cold temperature
When the plasma membrane was disrupted or lysed (necrosis), cytoplasmic LDH was released to the medium and its level was used as a biomarker for cell lysis or necrosis. The addition of rCLU to UW solution (Viaspan; Duramed Pharm Inc, Pomona, NY) prevented the cell lysis of cultured HUVECs in a dose-dependent manner, as evidenced by a significant decrease in LDH release from 73 ± 7% in HUVECs treated with UW solution alone (control) to 26 ± 8% in those with 0.5 mg/mL of rCLU or to 23 ± 2% with 1
Discussion
Cold ischemic injury, together with additional injury from rewarming or reperfusion, contributes to poor organ function in the immediate posttransplantation and subsequent rejection episodes.18, 19, 20 Therefore, the limitation of cold ischemic injury by optimizing cold preservation may improve the success of organ transplantation. Our previous study found that graft-expressing CLU renders resistance of donor hearts to cold ischemic injury in an experimental study.16 The present study shows
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2012, Biotechnology AdvancesCitation Excerpt :When Clusterin (CLU) a chaperonic protein was added, the results showed a reduction in donor heart injury during preservation at 4 °C before transplantation (Wyatt et al., 2009). Therefore, the presence of CLU added to the UW solution gives donor hearts greater resistance to cold ischemic injury (Guan et al., 2012). However, conventional refrigeration and freezing have their limitations, since they require storage at low temperatures and special transport conditions, as well as competent personnel (Taylor et al., 2004).
Perioperative ischaemic reperfusion injury and allograft function in the early post-transplantation period
2019, Interactive Cardiovascular and Thoracic SurgeryClusterin Reduces Cold Ischemia-Reperfusion Injury in Heart Transplantation Through Regulation of NF-kB Signaling and Bax/Bcl-xL Expression
2018, Cellular Physiology and BiochemistryCold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats
2017, American Journal of Translational ResearchThe CLU-files: Disentanglement of a mystery
2016, Biomolecular Concepts
Supported by the Centres of Excellence for Commercialization and Research and Natural Sciences and Engineering Council of Canada. Dr Li received the Postdoctoral Training Award from the Canadian Institutes of Health Research Training Program in Transplantation (Vancouver Coastal Health Research Institute).