Factors affecting human islet of Langerhans isolation yields

Toso, Christian; Oberholzer, José; Ris, Frédéric; Triponez, Frédéric; Bucher, Pascal Alain Robert; Demi̇rağ, A; Andereggen, E; Buehler, Leo Hans; Crétin, Nathalie; Fournier, B.; Majno, Pietro; Hong, Yeonhee; Lou, Jinning; Morel, Philippe

doi:10.1016/s0041-1345(01)02925-6

Cited by 66 publications

(52 citation statements)

References 10 publications

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“…Donor organ characteristics are reported in Table 1. Difference in age between study groups has no effect on yield (19). All organs carried minor tissue damage requiring repairing maneuvers prior to enzyme injection.…”

Section: Donor Characteristicsmentioning

confidence: 89%

Flexible Management of Enzymatic Digestion Improves Human Islet Isolation Outcome from Sub‐Optimal Donor Pancreata

Balamurugan

Chang

Fung

et al. 2003

American Journal of Transplantation

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Worldwide growing interest in reproducing the result of the Edmonton protocol in islet transplantation trials poses the problem of paucity of donors to supply sufficient amount of islets for clinical use. Improved outcomes include finding better ways to obtain higher yields from every donor organ processed and the possibility of extending islet isolation processing to glands of suboptimal quality. In order to optimize enzymatic digestion of marginal donor organs, we have modified the technique of tissue collection following enzymatic digestion of human pancreatic organs, allowing for reduced time of exposure of free islets to warm Liberase TM solution. Our results indicate that better controlled exposure to enzyme yields: (i) higher islet numbers; (ii) complete dissociation of all parts of pancreatic tissue; (iii) successful islet harvest from organs otherwise excluded. We also show that by limiting the exposure of free islets to enzyme solution, islet fragmentation and loss of insulin content are reduced. We further support evidence that enzymatic digestion may contribute to impairment of insulin secretory capacity of the islets in vitro during culture.

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Section: Donor Characteristicsmentioning

confidence: 89%

Flexible Management of Enzymatic Digestion Improves Human Islet Isolation Outcome from Sub‐Optimal Donor Pancreata

Balamurugan

Chang

Fung

et al. 2003

American Journal of Transplantation

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“…cause of death, length of intensive care). The predictive value of these non-specific criteria, derived from retrospective cohort analyses [3][4][5][6], remains limited, with the mean success rate of clinical islet isolation hardly surpassing 50% even in the most experienced centres [7,8].…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, the variability of human islet isolation outcome remains an exasperating and expensive issue in clinical islet transplantation [1]. Despite significant technical improvements, results remain highly dependent on donor characteristics and on the conditions of pancreas procurement and storage [3][4][5][6]. Potential donors are, therefore, habitually selected according to non-specific criteria derived from retrospective analysis of large series of human islet isolation [7].…”

Section: Introductionmentioning

confidence: 99%

Acute insulin response of donors is correlated with pancreatic islet isolation outcome in the pig

et al. 2005

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Aims/hypothesis: Unpredictability of islet isolation outcome remains a frustrating and costly issue in the clinical implementation of islet transplantation. The aim of this experimental study was to test the hypothesis that the donor's insulin secretory reserve, an in vivo surrogate of functional pancreatic mass, is correlated with the outcome of islet isolation. Methods: Insulin secretory reserve was evaluated in 28 healthy adult minipigs prior to pancreatectomy and islet isolation. Blood glucose and insulinaemia were measured before and 1, 3, 5, 10, 15, 30, 60 and 90 min after glucose infusion. Following total pancreatectomy, islet isolation was performed according to Ricordi's semi-automated method, and the total number of islets obtained was determined. Fasting blood glucose, insulinaemia, acute insulin response (AIR), maximal insulinaemia and the glucose decay constant (K G ) were calculated, and possible associations with the outcome of islet isolation were assessed. Results: AIR and maximal insulinaemia after glucose injection were correlated with the outcome of islet isolation (p<0.01). Mean values for AIR and maximal insulinaemia were significantly different between animals in which islet isolation was successful (n=11) vs those in which it was unsuccessful (n=17) (77.6±13.7 μU/ml vs 42.3±7.8 μU/ml, p<0.05; 144.7± 21.6 μU/ml vs 71.9±10.4 μU/ml, p<0.05, respectively). Conclusions/interpretation: This study suggests that the donor's pancreatic endocrine mass, as estimated by AIR, is a major determinant of the outcome of islet isolation in large mammals. Our results may explain the frustrating variability of human islet isolation outcome and could lead to a new approach for optimising the selection of brain-dead and/or living pancreas donors.

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“…In human situations, most recipients still need islet preparations isolated from more than one donor to provide a sufficient islet mass for achieving insulin independence [2,29]. With this study we intended to show that, with this new method, both quality and quantity of the islets obtained from one donor are sufficiently high for maintaining one diabetic recipient's insulin-independence.…”

Section: Discussionmentioning

confidence: 99%

Stable transplantation results of magnetically retracted islets: a novel method

et al. 2003

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Aims/hypothesis. Large quantities of pure viable donor islets are necessary for clinical transplantation. At present, low yields and low viability of pancreatic islets after transplantation necessitate the use of multiple donors for a single recipient. In this study an improved method for obtaining large quantities of pure viable islets of Langerhans for transplantation was developed in the rat. Methods. Islets of Langerhans were isolated from Albino Oxford rats. The donor pancreata were perfused in situ with iron oxide, which resulted in entrapment of iron particles in the capillaries of the islets. Subsequently, the islets were isolated by magnetic retraction. Islets obtained with this method were compared with islets obtained by density gradient-isolated islets with respect to yields, purity, and insulin production capacity. Islets isolated with the magnetic retraction method were transplanted under the renal capsule of streptozotocin-induced diabetic recipients. Blood-glucose levels in the recipients were monitored for 2 months after transplantation.Results. This method yielded more pure and viable islets than the conventional protocol. No contamination of exocrine tissue was observed after isolation. Furthermore, the islets isolated by magnetic retraction stained strongly positive for insulin during the entire observation period in vitro, and produced high amounts of insulin upon a challenge with glucose. The islets that were obtained by this new protocol were suitable for safe and effective transplantation. Conclusions/interpretation. We have shown that both the quantity and quality of islets obtained with this method were sufficient to induce insulin independence in a diabetic recipient using islets from only one donor. [Diabetologia (2004) 47:55-61]

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Factors affecting human islet of Langerhans isolation yields

Cited by 66 publications

References 10 publications

Flexible Management of Enzymatic Digestion Improves Human Islet Isolation Outcome from Sub‐Optimal Donor Pancreata

Flexible Management of Enzymatic Digestion Improves Human Islet Isolation Outcome from Sub‐Optimal Donor Pancreata

Acute insulin response of donors is correlated with pancreatic islet isolation outcome in the pig

Stable transplantation results of magnetically retracted islets: a novel method

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