BackgroundThis study compared the use of static cold storage versus continuous hypothermic machine perfusion in a cohort of kidney transplant recipients at high risk for delayed graft function (DGF).MethodsIn this national, multicenter, and controlled trial, 80 pairs of kidneys recovered from brain-dead deceased donors were randomized to cold storage or machine perfusion, transplanted, and followed up for 12 months. The primary endpoint was the incidence of DGF. Secondary endpoints included the duration of DGF, hospital stay, primary nonfunction, estimated glomerular filtration rate, acute rejection, and allograft and patient survivals.ResultsMean cold ischemia time was high but not different between the 2 groups (25.6 ± 6.6 hours vs 25.05 ± 6.3 hours, 0.937). The incidence of DGF was lower in the machine perfusion compared with cold storage group (61% vs. 45%, P = 0.031). Machine perfusion was independently associated with a reduced risk of DGF (odds ratio, 0.49; 95% confidence interval, 0.26-0.95). Mean estimated glomerular filtration rate tended to be higher at day 28 (40.6 ± 19.9 mL/min per 1.73 m2 vs 49.0 ± 26.9 mL/min per 1.73 m2; P = 0.262) and 1 year (48.3 ± 19.8 mL/min per 1.73 m2 vs 54.4 ± 28.6 mL/min per 1.73 m2; P = 0.201) in the machine perfusion group. No differences in the incidence of acute rejection, primary nonfunction (0% vs 2.5%), graft loss (7.5% vs 10%), or death (8.8% vs 6.3%) were observed.ConclusionsIn this cohort of recipients of deceased donor kidneys with high mean cold ischemia time and high incidence of DGF, the use of continuous machine perfusion was associated with a reduced risk of DGF compared with the traditional cold storage preservation method.
challenge. A strategy that has been gaining much attention is to bioengineer prevascularize tissue constructs that allow for immediate perfusion. We present the development of a large vascularized functional human liver construct that can be maintained for 30 days with high viability METHODS: Vascularized human liver tissue constructs of 1.5 cm in diameter and 6 cm in length were fabricated using an extrusionbased 3D printing system, seeded with hepatocytes (HepG2) in bulk hydrogel (alginate) and human umbilical vein endothelial cells (HUVECs) within the vascular channels. The alginate/HepG2 mixture was placed into a mold. A sacrificial gel (calcium chloride/HUVECs) was used to create vessels. Post printing, the samples were cured using calcium chloride and incubated at 37 C to liquefy the sacrificial gel. The liver tissue constructs were maintained in a media bath for 4 days, followed by media perfusion for 30 days using a peristaltic pump. The tissue samples were removed every 10 days and analyzed for cellular viability and biochemical functionality (albumin/bilirubin production). Immunohistochemistry was used to confirm the location of hepatocytes and endothelial cells.RESULTS: Alginate and calcium chloride was successfully used to fabricate constructs patterned with internal vascular channels running the entire length of the construct. The final constructs were cylindrical and maintained their structural integrity. The liver tissue samples showed high viability following fabrication and maintained a greater than 94 percent viability throughout the 30-day time point. The liver tissue constructs produced albumin and bilirubin at levels comparable to human liver tissue (assayed at 10, 20, and 30 days). In the retrieved constructs endothelial cells were identified on the vascular channel walls surrounded by hepatocytes in the hydrogel.CONCLUSIONS: We have successfully created large vascularized liver tissue constructs patterned with hollow channels using 3D bioprinting. The combination of perfusion and internal channels maintained high viability for 30 days. The liver tissue constructs produced albumin and bilirubin levels comparable to human liver tissue. This is a major step towards creating large vascularized functional liver tissue constructs that could be used for translational applications.
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