Sodium levels of human pancreatic donors are a critical factor for determination of islet efficacy and survival

Abstract

Organs from hypernatremia (elevated Na+) donors when used for transplantation have had dismal outcomes. However, islet isolation from hypernatremic donors for both transplantation and research applications has not yet been investigated. A retrospective analysis of in vivo and in vitro islet function studies was performed on islets isolated from hypernatremic (serum sodium levels≥160 meq/l) and normal control (serum sodium levels≤155 meq/l) donors. Twelve isolations from 32 hypernatremic and 53 isolations from 222 normal donors were randomly transplanted into diabetic NOD Scid mice. Sodium levels upon pancreas procurement were significantly elevated in the hypernatremia group (163.5±0.6 meq/l) compared with the normal control group (145.9±0.4 meq/l) (P<0.001). The postculture islet recovery rate was significantly lower in the hypernatremia (59.1±3.8%) group compared with the normal (73.6±1.8%) group (P=0.005). The duration of hypernatremia was inversely correlated with the recovery rate (r2=0.370, P<0.001). Furthermore, the percentage of successful graft function when transplanted into diabetic NOD Scid mice was significantly lower in the hypernatremia (42%) group compared with the normal control (85%) group (P<0.001). The ability to predict islet graft function posttransplantation using donor sodium levels and duration of hypernatremia was significant (ROC analysis, P=0.022 and 0.042, respectively). In conclusion, duration of donor hypernatremia is associated with reduced islet recovery postculture. The efficacy of islets from hypernatremia donors diminished when transplanted into diabetic recipients.

Donor Hypernatremia is Not Related with the Duration of Postoperative Mechanical Ventilation, Primary Graft Dysfunction, or Long-Term Outcome Following Lung Transplantation

“…Donor characteristics (age, sex, smoking, cause of death, and PaO 2 /FiO 2 ratio) were taken from the Eurotransplant report form, including the highest level of serum sodium from the donor on the day of donation. The 3 study groups were based on donor hypernatremia defined as: normonatremia as serum sodium ≥145 mmol/L, moderate donor hypernatremia as 145–154 mmol/L, and severe donor hypernatremia as ≥155 mmol/L, which corresponds with the threshold used in previous studies in patients after cardiac or pancreatic islets transplantations [ 6 , 8 ].…”

Prophylactically Decontaminating Human Islet Product for Safe Clinical Application

“… 29 , 30 Although, whole organ transplantation is not overseen by the FDA, pancreatic islet transplantation is strictly regulated due to the complexity of the preparation of the final product. 11 In compliance with FDA guidelines and regulations, the islet isolation process is completed without using antibiotics that may cause an allergic reaction in certain transplant recipients. Antimicrobial agents are only used in the initial step of pancreas decontamination upon receiving the organ to prevent carrying over the microbial contamination into the islet final product.…”

“… 8 - 10 The contamination issue is further exacerbated in islet isolation, which involves multiple steps, including preservation of the whole pancreas with a portion of the duodenum and/or spleen attached, trimming and decontamination of pancreas, perfusion of enzyme, digestion, collection, washing of pancreatic tissue, purification, culturing, and collection of islets. 11 Although, the process of manufacturing islet final product is carried out in a current good manufacturing practice (cGMP) facility, the risk of introducing contamination at any stage of the procedure still remains. 12 - 14 Aside from the media used in pancreas decontamination, all other solutions used throughout the pancreas preservation and islet isolation process are prepared within the cGMP facility without addition of antimicrobial agents to prevent a potential allergic reaction of the recipient.…”

Evaluation of collagenase gold plus BP protease in isolating islets from human pancreata

“…Islet transplantation into NOD scid mice was carried out as previously developed method. 8 Briefly, male NOD scid mice (Jackson Laboratory, Bar Harbor, ME, USA) that were 10–12 weeks of age were used as islet recipients. Mice were housed at the Animal Resources Center, Beckman Research Institute of the City of Hope.…”