Using HTK for Prolonged Pancreas Preservation Prior to Human Islet Isolation

Caballero-Corbalan, José; Brandhorst, Heide; Malm, Helene; Felldin, Marie; Foss, Aksel; Salmela, K.; Tibell, Annika; Tufveson, Gunnar; Korsgren, Olle; Brandhorst, Daniel

doi:10.1016/j.jss.2011.03.012

Cited by 20 publications

(16 citation statements)

References 36 publications

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“…Besides donor selection and optimization of the pancreas preservation and isolation process, several approaches have been made to precondition islets before transplantation (43)(44)(45)(46)(47). Conditioning of pancreatic islets with GHRH agonist JI-36 improves beta-cell survival and metabolic function in vivo mainly due to a reduction in apoptosis and preservation of the proliferative capacity of the islet cells (40).…”

Section: Discussionmentioning

confidence: 99%

Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist

Ludwig

Rotem

Schmid

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

169

129

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Islet transplantation is a feasible therapeutic alternative for metabolically labile patients with type 1 diabetes. The primary therapeutic target is stable glycemic control and prevention of complications associated with diabetes by reconstitution of endogenous insulin secretion. However, critical shortage of donor organs, gradual loss in graft function over time, and chronic need for immunosuppression limit the indication for islet transplantation to a small group of patients. Here we present a promising approach to address these limitations by utilization of a macrochamber specially engineered for islet transplantation. The s.c. implantable device allows for controlled and adequate oxygen supply and provides immunological protection of donor islets against the host immune system. The minimally invasive implantable chamber normalized blood glucose in streptozotocin-induced diabetic rodents for up to 3 mo. Sufficient graft function depended on oxygen supply. Pretreatment with the growth hormone-releasing hormone (GHRH) agonist, JI-36, significantly enhanced graft function by improving glucose tolerance and increasing β-cell insulin reserve in rats thereby allowing for a reduction of the islet mass required for metabolic control. As a result of hypervascularization of the tissue surrounding the device, no relevant delay in insulin response to glucose changes has been observed. Consequently, this system opens up a fundamental strategy for therapy of diabetes and may provide a promising avenue for future approaches to xenotransplantation. treatment of diabetes | immune isolation | beta cells

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Section: Discussionmentioning

confidence: 99%

Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist

Ludwig

Rotem

Schmid

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

169

129

View full text Add to dashboard Cite

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“…Hence, it is important to evaluate the characteristics of donors that may influence the outcomes of islet isolation (36). According to published studies, critical donor factors that affect islet isolation include age (31,35,52,57), cause of death (16,31,57), cold ischemia time (7,10,41), body mass index (BMI) (9,20,26,54), and the acute insulin response to arginine (22). The aforementioned factors have been widely reported; however, donor hemodynamic and biochemical parameters have not been investigated thoroughly (14).…”

mentioning

confidence: 99%

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

Valiente

Bilbao

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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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.

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“…Various comparisons have been performed between, for example, the classical Belzer ® UW solution and modifications by perfluorohexyloctan, perfluorodecalin and perfluorocarbon, 22,23 or the addition of hydroxyethyl starch, 8 Belzer ® UW solution in comparison with Custodiol ® -HTK solution for solid organ transplantation. 11,18,21,24,25 These studies demonstrate that OPS has strong influence on organs of different origin, their quality, and the success of islet isolation. Thus, this topic has been addressed specifically for the preservation of Goettingen minipig pancreata with additional focus on prolonged ischemia time.…”

Section: Discussionmentioning

confidence: 71%

Production of high‐quality islets from goettingen minipigs: Choice of organ preservation solution, donor pool, and optimal cold ischemia time

Steffen

Kiss

Schmid

et al. 2017

Xenotransplantation

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In summary, Custodiol -HTK solution should be preferred over Belzer UW solution for the preservation of pancreata from porcine origin. Custodiol -HTK allows for maintaining islet viability and promotes reproducible isolation outcome and survival even after longer CIT. The usage of retired breeder animals over young animals for islet isolation is highly advisable to yield high quality and quantity.

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Using HTK for Prolonged Pancreas Preservation Prior to Human Islet Isolation

Cited by 20 publications

References 36 publications

Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist

Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist

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

Production of high‐quality islets from goettingen minipigs: Choice of organ preservation solution, donor pool, and optimal cold ischemia time

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