Islet Transplantation: Factors in Short-Term Islet Survival

Deters, Natasha; Stokes, Rebecca; Gunton, Jenny E.

doi:10.1007/s00005-011-0143-0

Cited by 34 publications

(17 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Native pancreatic beta cells have high rates of oxidative metabolism to meet the demand of insulin production and secretion [5], and even moderately decreased levels of oxygen have been shown to inhibit insulin release [6]. Hypoxia after transplantation is a major (albeit not the only) contributor to the dramatic drop of viable beta cells (nonencapsulated) that occurs in the immediate period following transplantation [7–10]. A negative impact of the—inevitable—hypoxia during the immediate period following transplantation could possibly be worsened by encapsulation, since the distance of diffusion for oxygen could be greater in encapsulated versus nonencapsulated islets (or amassed beta cells) [11, 12], and a negative effect of clustering of islets may occur [13].…”

Section: Introductionmentioning

confidence: 99%

Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

Hals

Rokstad

Strand

et al. 2013

Journal of Diabetes Research

View full text Add to dashboard Cite

Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8 ± 3.5% in encapsulated and 42.9 ± 5.2% in nonencapsulated islets (P < 0.2). Nonencapsulated islets released 37.7% (median) more HMGB1 compared to encapsulated islets after hypoxic culture conditions (P < 0.001). Glucose-induced insulin release was marginally affected by hypoxia. Basal oxygen consumption was equally reduced in encapsulated and nonencapsulated islets, by 22.0 ± 6.1% versus 24.8 ± 5.7%. Among 27 tested cytokines/chemokines, hypoxia increased the secretion of IL-6 and IL-8/CXCL8 in both groups of islets, whereas an increase of MCP-1/CCL2 was seen only with nonencapsulated islets. Conclusion. Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation.

show abstract

Section: Introductionmentioning

confidence: 99%

Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

Hals

Rokstad

Strand

et al. 2013

Journal of Diabetes Research

View full text Add to dashboard Cite

show abstract

“…Despite all the advances in ICT, several significant issues, including multiple donor requirements, side effects associated with immunosuppressive drugs, and maintaining long-term islet survival, limit the procedure and outcome of ICT. [1][2][3][4][5] Pancreatic islets compose a small portion of the whole pancreas; the isolation process aims to remove the exocrine tissue through enzymatic digestion of the extracellular matrix (ECM) and mechanical separation followed by density gradient. 1 Islet isolation digests peripheral ECM and periinsular basement membrane, interrupting oxygen and nutrient delivery, 6,7 and compromises islet survival, reducing islet yield.…”

mentioning

confidence: 99%

“…10 Despite their value in preventing islet allorejection, immunosuppressants can directly contribute to β-cell toxicity. 1,11,12 One option to avoid using systemic immunosuppressive regimens is to locally induce an immunosuppressive factor, indoleamine 2,3-dioxygenase (IDO), the first and ratelimiting enzyme in tryptophan catabolism pathway. 13 Indoleamine 2,3-dioxygenase generates a microenvironment, low in tryptophan and rich in kynurenine metabolites, that is selectively toxic to T-cells, whereas allogeneic islets remain intact.…”

mentioning

confidence: 99%

Immunoprotection and Functional Improvement of Allogeneic Islets in Diabetic Mice, Using a Stable Indoleamine 2,3-Dioxygenase Producing Scaffold

Hosseini‐Tabatabaei

Jalili²,

Khosravi‐Maharlooei³

et al. 2015

Transplantation

View full text Add to dashboard Cite

show abstract

“…This lack of absolute β-cell volume undeniably contributes to a gradual return to insulin therapy for many of the patients. β-cells are relatively susceptible to stress induced apoptosis, which contributes to their own demise [7], [31], [36]. Islets post-transplantation are exposed to various specific stresses including hyperglycaemia, IBMIR (instant blood mediated inflammatory reaction), cytokines and free radicals, lack of adequate nutrients, hypoxia and immune-mediated rejection (6).…”

Section: Discussionmentioning

confidence: 99%

Deletion of ARNT (Aryl Hydrocarbon Receptor Nuclear Translocator) in β-Cells Causes Islet Transplant Failure with Impaired β-Cell Function

et al. 2014

Self Cite

View full text Add to dashboard Cite

BackgroundReplacing β-cells by islet-transplantation can cure type 1 diabetes, but up to 70% of β-cells die within 10 days of transplantation. ARNT (Aryl hydrocarbon Receptor Nuclear Translocator) regulates β-cell function, and potentially survival. Lack of ARNT impairs the ability of β-cells to respond to physiological stress and potentiates the onset of diabetes, but the exact role of ARNT in graft outcome is unknown.AimTo investigate the effect of β-cell deletion of ARNT on graft outcomes.MethodsIslets were isolated from donor mice which had β-cell specific ARNT-deletion (β-ARNT) or littermate floxed controls. The islets were transplanted into diabetic SCID recipients in ratios of (a) 3 donors: 1 recipient, (b) 1 donor: 1 recipient or (c) ½ of the islets from 1 donor: 1 recipient. After 28 days, the kidney containing the graft was removed (nephrectomy) to exclude regeneration of the endogenous pancreas.ResultsIn the supra-physiological-mass model (3∶1), both groups achieved reasonable glycaemia, with slightly higher levels in β-ARNT-recipients. In adequate-mass model (1∶1), β-ARNT recipients had poor glucose control versus floxed-control recipients and versus the β-ARNT donors. In the low-β-cell-mass model (½:1) β-ARNT transplants completely failed, whereas controls had good outcomes. Unexpectedly, there was no difference in the graft insulin content or β-cell mass between groups indicating that the defect was not due to early altered β-cell survival.ConclusionOutcomes for islet transplants lacking β-cell ARNT were poor, unless markedly supra-physiological masses of islets were transplanted. In the 1∶1 transplant model, there was no difference in β-cell volume. This is surprising because transplants of islets lacking one of the ARNT-partners HIF-1α have increased apoptosis and decreased islet volume. ARNT also partners HIF-2α and AhR (aryl hydrocarbon receptor) to form active transcriptional complexes, and further work to understand the roles of HIF-2α and AhR in transplant outcomes is needed.

show abstract

Islet Transplantation: Factors in Short-Term Islet Survival

Cited by 34 publications

References 123 publications

Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

Immunoprotection and Functional Improvement of Allogeneic Islets in Diabetic Mice, Using a Stable Indoleamine 2,3-Dioxygenase Producing Scaffold

Deletion of ARNT (Aryl Hydrocarbon Receptor Nuclear Translocator) in β-Cells Causes Islet Transplant Failure with Impaired β-Cell Function

Contact Info

Product

Resources

About