Technical aspects of islet preparation and transplantation

Lakey, Jonathan R.T.; Burridge, Philip W.; Shapiro, A.M. James

doi:10.1111/j.1432-2277.2003.tb00361.x

Cited by 93 publications

(44 citation statements)

References 198 publications

(11 reference statements)

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“…The inflammatory response activated in the pancreas at the time of isolation and implantation is secondary to multiple events, such as donor brain death, pancreas procurement, organ preservation, islet isolation and early stages of transplantation [30][31][32]. Interestingly, recent data suggest that JNK may represent a key target factor of such an inflammatory response [1,33,34], since activation of JNK during islet isolation and engraftment is detrimental to islet cell survival [4,5,9,24].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of c-jun N terminal kinase (JNK) improves functional beta cell mass in human islets and leads to AKT and glycogen synthase kinase-3 (GSK-3) phosphorylation

et al. 2007

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Aims/hypothesis Activation of c-jun N-terminal kinase (JNK) has been described in islet isolation and engraftment, making JNK a key target in islet transplantation. The objective of this study was to investigate if JNK inhibition with a cellpermeable TAT peptide inhibitor (L-JNKI) protects functional beta cell mass in human islets and affects AKT and its substrates in islet cells. Methods The effect of L-JNKI (10 μmol/l) on islet count, mitochondrial membrane potential, glucose-stimulated insulin release and phosphorylation of both AKT and its substrates, as well as on reversal of diabetes in immunodeficient diabetic Nu/Nu mice was studied. Results In vitro, L-JNKI reduced the islet loss in culture and protected from cell death caused by acute cytokine exposure. In vivo, treatment of freshly isolated human islets and diabetic Nu/Nu mice recipients of such islets resulted in improved functional beta cell mass. We showed that L-JNKI activates AKT and downregulates glycogen synthase kinase-3 beta (GSK-3B) in human islets exposed to cytokines, while other AKT substrates were unaffected, suggesting that a specific AKT/GSK-3B regulation by L-JNKI may represent one of its mechanisms of cytoprotection. Conclusions/interpretation In conclusion, we have demonstrated that targeting JNK in human pancreatic islets results in improved functional beta cell mass and in the regulation of AKT/GSK3B activity.

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Section: Discussionmentioning

confidence: 99%

Inhibition of c-jun N terminal kinase (JNK) improves functional beta cell mass in human islets and leads to AKT and glycogen synthase kinase-3 (GSK-3) phosphorylation

et al. 2007

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“…Contamination of islets by acinar cells may lead to a high level of proteases that will hamper islet integrity and functionality (O'Dowd 2009) and could cause serious postsurgical complications following intraportal transplantation (Lakey et al 2003;Gray et al 1988). In this study we aimed to compare the quality of islets obtained by an established method of islet purification, Histopaque, with an appealing alternative one, filtration, although some modifications of the original protocol were needed.…”

Section: Discussionmentioning

confidence: 99%

“…However, one-third of the islets are lost with filtration compared to Histopaque, and more animals are needed, so each laboratory should decide which method is more suitable according to their aims or economical situation. It is currently accepted that mouse and human islets differ in their anatomy and functionality (Cabrera et al 2006) and that the human pancreas is more fibrous and dense than in rodents (Lakey et al 2003;O'Dowd 2009). But both human and rodent islets are in the same range of size (Kim et al 2009), thus making size-based purification like filtration a method of interest also for human islet purification.…”

Section: Discussionmentioning

confidence: 99%

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Filtration is a time-efficient option to Histopaque, providing good-quality islets in mouse islet isolation

Ramírez-Domínguez

Castaño

2014

Cytotechnology

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Pancreatic islet transplantation is a promising therapy for Type I Diabetes. For many years the method used worldwide for islet purification in both rodent and human islet isolation has been Ficoll-based density gradients, such as Histopaque. However, it is difficult to purify islets in laboratories with staff limitations when large scale isolations are required. We hypothesized that filtration could be a more simple and fast alternative to obtain good quality islets. Four separate islet isolations were performed per method, comparing filtration and Histopaque purification with handpicking as the gold standard method for islet purity. Different parameters of quality were assessed: yield in number of islets per pancreas, purity by dithizone staining, viability by Fluorescein Diacetate/ Propidium Iodide vital staining and in vitro functionality assessed by Glucose Stimulated Insulin Secretion. Time efficiency and cost were also analyzed. The overall quality of the islets obtained both by Histopaque and filtration was good. Filtration saved almost 90 % of the time consumed by Histopaque purification, and was also cheaper. However, one-third of the islets were lost. Since human and rodent islets share similar size but different density, filtration appears as a purification method with potential interest in translation to clinic.

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“…Subsequent discoveries related to enzymatic digestion and tissue purification paved the way for successful large-scale human islet isolation. The intraductal injection of collagenase proved an effective method for successful islet isolation from large animals and humans 4 . The first clinical islet transplant was performed at the University of Minnesota, USA by Najarian et al 5 .…”

Section: History Of Pancreatic Islet Transplantation For Type-1 Diabetesmentioning

confidence: 99%

Clinical Islet Cell Transplantation – Recent Advances

Saravanan¹,

Loganathan²,

Naziruddin³

et al. 2017

Current Science

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Type-1 diabetes mellitus (T1DM) caused by autoimmune destruction of insulin-producing beta-cells essentially requires treatment with exogenous insulin therapy. Despite the education, technology and improvements in insulin formulations, patients face the ongoing life-threatening hypoglycaemia with poor quality of life as well as progressive disease leading to microand macro-vascular complications of diabetes. Islet transplantation offers an alternative therapeutic option for these patients. In this review, we discuss the recent advancements in this field tracking from the history of pancreatic islet transplantation to the present-day challenges of clinical islet cell transplantation. We summarize the cutting-edge clinical research with special reference to the results of current trials, including Clinical Islet Transplant Consortium, improvements in immunosuppressive protocols, the need for beta-cell replacement therapies, including the application of induced pluripotent stem cells and mesenchymal stem cells.

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Technical aspects of islet preparation and transplantation

Cited by 93 publications

References 198 publications

Inhibition of c-jun N terminal kinase (JNK) improves functional beta cell mass in human islets and leads to AKT and glycogen synthase kinase-3 (GSK-3) phosphorylation

Inhibition of c-jun N terminal kinase (JNK) improves functional beta cell mass in human islets and leads to AKT and glycogen synthase kinase-3 (GSK-3) phosphorylation

Filtration is a time-efficient option to Histopaque, providing good-quality islets in mouse islet isolation

Clinical Islet Cell Transplantation – Recent Advances

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