title: Hyperbranched polyglycerol as a colloid in cold organ preservation solutions.
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.
authors.affiliation: Department of Urologic Sciences, the University of British Columbia, Vancouver, BC, Canada; Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Sihai
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Urologic Sciences, the University of British Columbia, Vancouver, BC, Canada.
authors.forename: Qiunong
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Centre for Blood Research, and the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Irina
authors.initials: I
authors.lastname: Chafeeva
authors.affiliation: Centre for Blood Research, and the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Chemistry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Brooks
authors.affiliation: Department of Urologic Sciences, the University of British Columbia, Vancouver, BC, Canada.
authors.forename: Christopher Y C
authors.initials: CY
authors.lastname: Nguan
authors.affiliation: Centre for Blood Research, and the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Chemistry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jayachandran N
authors.initials: JN
authors.lastname: Kizhakkedathu
authors.affiliation: Department of Urologic Sciences, the University of British Columbia, Vancouver, BC, Canada.
authors.forename: Caigan
authors.initials: C
authors.lastname: Du
mesh_terms: D000818:Animals; D003102:Colloids; D015925:Cryopreservation / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology; D005990:Glycerol; D006321:Heart; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D051379:Mice; D009206:Myocardium / Q000166:cytology; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D011108:Polymers; D051381:Rats
chemical_list: D003102:Colloids; D019188:Organ Preservation Solutions; D011108:Polymers; C043941:polyglycerol; D005990:Glycerol