Abstract
Hydroxyethyl starch (HES) is a common colloid in organ preservation solutions, such as in University of Wisconsin (UW) solution, for preventing graft interstitial edema and cell swelling during cold preservation of donor organs. However, HES has undesirable characteristics, such as high viscosity, causing kidney injury and aggregation of erythrocytes. Hyperbranched polyglycerol (HPG) is a branched compact polymer that has low intrinsic viscosity. This study investigated HPG (MW-0.5 to 119 kDa) as a potential alternative to HES for cold organ preservation. HPG was synthesized by ring-opening multibranching polymerization of glycidol. Both rat myocardiocytes and human endothelial cells were used as an in vitro model, and heart transplantation in mice as an in vivo model. Tissue damage or cell death was determined by both biochemical and histological analysis. HPG polymers were more compact with relatively low polydispersity index than HES in UW solution. Cold preservation of mouse hearts ex vivo in HPG solutions reduced organ damage in comparison to those in HES-based UW solution. Both size and concentration of HPGs contributed to the protection of the donor organs; 1 kDa HPG at 3 wt% solution was superior to HES-based UW solution and other HPGs. Heart transplants preserved with HPG solution (1 kDa, 3%) as compared with those with UW solution had a better functional recovery, less tissue injury and neutrophil infiltration in syngeneic recipients, and survived longer in allogeneic recipients. In cultured myocardiocytes or endothelial cells, significantly more cells survived after cold preservation with the HPG solution than those with the UW solution, which was positively correlated with the maintenance of intracellular adenosine triphosphate and cell membrane fluidity. In conclusion, HPG solution significantly enhanced the protection of hearts or cells during cold storage, suggesting that HPG is a promising colloid for the cold storage of donor organs and cells in transplantation.
Highlights
Cold preservation of donor organs, tissues and cells with a specialized solution is a common strategy to minimize ischemic injury prior to transplantation, and so far many different preservation solutions have been developed for this purpose [1]
Two other important limitations associated with hydroxyethyl starch pentafraction (HES) in University of Wisconsin (UW) solution have been suggested: (i) it increases the viscosity of the solution, resulting in an increase in vascular resistance of donor organs to the initial flushing/perfusion that could shorten graft survival [17, 18]; and (ii) it causes the hyperaggregation of human red blood cells (RBCs) due to the adsorption of HES to RBCs [19,20,21], which may result in stasis of blood and incomplete washout from donor organs before transplantation
Data from this study clearly show that the Hyperbranched polyglycerol (HPG) solution in comparison to the standard UW solution is more effective in reducing cold ischemic injury in donor hearts
Summary
Cold preservation of donor organs, tissues and cells with a specialized solution is a common strategy to minimize ischemic injury prior to transplantation, and so far many different preservation solutions have been developed for this purpose [1]. Inclusion of HES is essential to counteract graft interstitial edema and endothelial cell swelling for improving viability and outcomes of donor organ preservation [9, 10], but it may have negative effects on its application as a cold organ preservation solution for transplantation. Two other important limitations associated with HES in UW solution have been suggested: (i) it increases the viscosity of the solution, resulting in an increase in vascular resistance of donor organs to the initial flushing/perfusion that could shorten graft survival [17, 18]; and (ii) it causes the hyperaggregation of human red blood cells (RBCs) due to the adsorption of HES to RBCs [19,20,21], which may result in stasis of blood and incomplete washout from donor organs before transplantation. There is an unmet need for an alternative colloid that is superior to HES in terms its biocompatibility as well as for maximally limiting donor organ injury during organ procurement or preservation
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