scholarly journals Induction of Protective Genes Leads to Islet Survival and Function

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Hongjun Wang ◽  
Christiane Ferran ◽  
Chiara Attanasio ◽  
Fulvio Calise ◽  
Leo E. Otterbein
Keyword(s):  
Islet Transplantation ◽  
Immunosuppressive Drugs ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Immune Rejection ◽  
Necrosis Factor Alpha ◽  
Protective Genes ◽  
Rejection Response ◽  
And Function ◽  
Islet Survival

Islet transplantation is the most valid approach to the treatment of type 1 diabetes. However, the function of transplanted islets is often compromised since a large number ofβcells undergo apoptosis induced by stress and the immune rejection response elicited by the recipient after transplantation. Conventional treatment for islet transplantation is to administer immunosuppressive drugs to the recipient to suppress the immune rejection response mounted against transplanted islets. Induction of protective genes in the recipient (e.g., heme oxygenase-1 (HO-1), A20/tumor necrosis factor alpha inducible protein3 (tnfaip3), biliverdin reductase (BVR), Bcl2, and others) or administration of one or more of the products of HO-1 to the donor, the islets themselves, and/or the recipient offers an alternative or synergistic approach to improve islet graft survival and function. In this perspective, we summarize studies describing the protective effects of these genes on islet survival and function in rodent allogeneic and xenogeneic transplantation models and the prevention of onset of diabetes, with emphasis on HO-1, A20, and BVR. Such approaches are also appealing to islet autotransplantation in patients with chronic pancreatitis after total pancreatectomy, a procedure that currently only leads to 1/3 of transplanted patients being diabetes-free.

scholarly journals Extra-Hepatic Islet Transplantation

2018 ◽  
Vol 27 (8) ◽  
pp. 1289-1293 ◽  
Author(s):  
Anaïs Schaschkow ◽  
Séverine Sigrist ◽  
Carole Mura ◽  
Caroline Dissaux ◽  
Karim Bouzakri ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Cell Therapy ◽  
Islet Transplantation ◽  
Graft Function ◽  
Surgical Techniques ◽  
Diabetic Rats ◽  
C Peptide ◽  
And Function ◽  
Islet Survival

Following the tremendous development of hydrogels for cell therapy, there is now a growing need for surgical techniques to validate in vivo scaffold benefits for islet transplantation. Therefore, we propose a newly designed surgical procedure involving the injection of hydrogel-embedded pancreatic islets in the omentum, which is considered a favorable environment for cell survival and function. Our technique, called h-Omental Matrix Islet filliNG (hOMING) was designed to test the benefits of hydrogel on islet survival and function in vivo. Islets were implanted in the omentum of diabetic rats using the hOMING technique and alginate as an islet carrier. Blood glucose and C-peptide levels were recorded to assess graft function. After 2 months, grafts were explanted and studied using insulin and vessel staining. All rats that underwent hOMING exhibited graft function characterized by a glycemia decrease and a C-peptidemia increase ( P < 0.001 compared with preoperative levels). Furthermore, hOMING appeared to preserve islet morphology and insulin content and allowed the proper revascularization of grafted islets. The results suggest that hOMING is a viable and promising approach to test in vivo the benefits of hydrogel administration for islet transplantation into the omental tissue.

scholarly journals Beta-cell function and human islet transplantation: can we improve?

2021 ◽  
Author(s):  
Jennifer Chen ◽  
Jenny E Gunton
Keyword(s):  
Islet Transplantation ◽  
Cell Function ◽  
Therapeutic Option ◽  
Human Islets ◽  
Post Transplantation ◽  
Human Islet Transplantation ◽  
And Function ◽  
Islet Survival

Islet transplantation, a therapeutic option to treat type 1 diabetes, is not yet as successful as whole-pancreas transplantation as a treatment for diabetes. Mouse models are commonly used for islet research. However, it is clear disparities exist between islet transplantation outcomes in mice and humans. Given the shortage of transplant-grade islets, it is crucial that we further our understanding of factors that determine long-term islet survival and function post-transplantation. In turn, that may lead to new therapeutic targets and strategies that to improve transplant outcomes. Here, we summarise the current landscape in clinical transplantation, highlight underlying similarities and differences between mouse and human islets, and review interventions that are being considered to create a new pool of β-cells for clinical application.

scholarly journals Protective Effects of the Third Generation Vasodilatory Βeta - Blocker Nebivolol against D-Galactosamine - Induced Hepatorenal Syndrome in Rats

2017 ◽  
Vol 5 (7) ◽  
pp. 880-892 ◽  
Author(s):  
Ahmed Atwa ◽  
Rehab Hegazy ◽  
Rania Mohsen ◽  
Neamat Yassin ◽  
Sanaa Kenawy
Keyword(s):  
Hepatorenal Syndrome ◽  
Histopathological Examination ◽  
Serum Levels ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Advanced Liver Cirrhosis ◽  
Factor Alpha

BACKGROUND: Renal dysfunction is very common in patients with advanced liver cirrhosis and portal hypertension. The development of renal failure in the absence of clinical, anatomical or pathological causes renal of failure is termed hepatorenal syndrome (HRS).AIM: The present study was constructed to investigate the possible protective effects of nebivolol (Nebi) against D-galactosamine (Gal)-induced HRS in rats.MATERIAL AND METHODS: Rats were treated with Nebi for ten successive days. On the 8th day of the experiment, they received a single dose of Gal. Serum levels of Cr, BUN, Na+ and K+ as well as AST, ALT, total bilirubin (TB), NH3 and endothelin-1 (ET-1) were determined following Gal administration. Moreover, renal and liver contents of MDA, GSH, F2-isoprostanes (F2-IPs), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-кB), total nitric oxide (NO), in addition to activities of caspase-3 (Cas-3), heme oxygenase-1 (HO-1), inducible and endothelial NO synthase (iNOS and eNOS) enzymes were also assessed. Finally, histopathological examination was performed.RESULTS: Nebi attenuated Gal-induced renal and hepatic dysfunction. It also decreased the Gal-induced oxidative stress and inflammatory recruitment.CONCLUSION: Results demonstrated both nephroprotective and hepatoprotective effects of Nebi against HRS and suggested a role of its antioxidant, anti-inflammatory, anti-apoptotic and NO-releasing properties.

scholarly journals Cryopreserved Alginate-Encapsulated Islets Can Restore Euglycemia in a Diabetic Animal Model Better than Cryopreserved Non-encapsulated Islets

Cell Medicine ◽  
2019 ◽  
Vol 11 ◽  
pp. 215517901987664 ◽  
Author(s):  
Greg G Kojayan ◽  
Antonio Flores ◽  
Shiri Li ◽  
Michael Alexander ◽  
Jonathan RT Lakey
Keyword(s):  
Islet Transplantation ◽  
Stimulation Index ◽  
Survival Function ◽  
Diabetic Animal ◽  
High Variability ◽  
Glucose Test ◽  
And Function ◽  
Islet Survival ◽  
Cryopreservation Protocol ◽  
Better Than

Islet transplantation has been shown to restore normoglycemia clinically. One of the current limitations to the widespread clinical use of islet transplantation is culturing and preserving more than 1 million islet equivalents in preparation for transplant. One possible solution is to bank frozen islets and use them when needed. Although promising, the standard islet freezing protocol introduces stress and cell death, resulting in high variability of islet quality post thawing. This study aimed to develop an improved cryopreservation protocol using alginate-encapsulated islets to improve islet survival and function for future transplants. Our data showed that encapsulation improved islet survival and function after thawing the frozen islets. Frozen encapsulated islets have an islet yield recovery of 84% when compared to non-encapsulated islets at 72% after thawing. Post-thaw viability was 78% for non-encapsulated islets compared to 88% for encapsulated islets. The stimulation index values after a static glucose test following thawing were 1.9 ± 0.5, 2.9 ± 0.1, and 3.3 ± 0.3 for the non-encapsulated, 1.75% alginate, and 2.5% alginate groups, respectively. In a transplant study, the mice that received 1.75% alginate-encapsulated cryopreserved islets achieved normoglycemia on average 5 days after transplant. In comparison, control mice that received fresh islets took 4 days, while those receiving unencapsulated cryopreserved islets took 18 days. In conclusion, encapsulating islets in 1.75% alginate prior to freezing was shown to improve islet survival, function post thawing, and graft response significantly when compared to islets frozen without encapsulation.

scholarly journals Amniotic Membrane Extract Protects Islets From Serum-Deprivation Induced Impairments and Improves Islet Transplantation Outcome

2020 ◽  
Vol 11 ◽  
Author(s):  
Zhaoming Yang ◽  
Xiaohang Li ◽  
Chengshuo Zhang ◽  
Ning Sun ◽  
Tingwei Guo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Islet Transplantation ◽  
Amniotic Membrane ◽  
Blood Glucose Control ◽  
Serum Deprivation ◽  
Erk Signaling ◽  
Membrane Extract ◽  
And Function ◽  
Islet Survival

Islet culture prior to transplantation is a standard practice in many transplantation centers. Nevertheless, the abundant islet mass loss and function impairment during this serum-deprivation culture period restrain the success of islet transplantation. In the present study, we used a natural biomaterial derived product, amniotic membrane extract (AME), as medium supplementation of islet pretransplant cultivation to investigate its protective effect on islet survival and function and its underlying mechanisms, as well as the engraftment outcome of islets following AME treatment. Results showed that AME supplementation improved islet viability and function, and decreased islet apoptosis and islet loss during serum-deprived culture. This was associated with the increased phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway. Moreover, transplantation of serum-deprivation stressed islets that were pre-treated with AME into diabetic mice revealed better blood glucose control and improved islet graft survival. In conclusion, AME could improve islet survival and function in vivo and in vitro, and was at least partially through increasing phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway.

scholarly journals PROMOTING EFFICACY OF ISLET TRANSPLANTATION BY ENHANCING ISLET SURVIVAL AND FUNCTION USING A FIBROBLAST POPULATED COLLAGEN SCAFFOLD.

2010 ◽  
Vol 90 ◽  
pp. 1020
Author(s):  
Baradar R. jalili ◽  
A. Moeen ◽  
A. Hosseini-tabatabaei ◽  
Z. Ao ◽  
G. Warnock ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Collagen Scaffold ◽  
And Function ◽  
Islet Survival

scholarly journals Protective Effect of Psoralea corylifolia L. Seed Extract against Palmitate-Induced Neuronal Apoptosis in PC12 Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yunkyoung Lee ◽  
Hee-Sook Jun ◽  
Yoon Sin Oh
Keyword(s):  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Marker Genes ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Protective Effects ◽  
Psoralea Corylifolia ◽  
Antioxidant Genes ◽  
Bax Protein

The extract of Psoralea corylifolia seeds (PCE) has been widely used as a herbal medicine because of its beneficial effect on human health. In this study, we investigated the protective effects and molecular mechanisms of PCE on palmitate- (PA-) induced toxicity in PC12 cells, a neuron-like cell line. PCE significantly increased cell viability in PA-treated PC12 cells and showed antiapoptotic effects, as evidenced by decreased expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, and bax protein as well as increased expression of bcl-2 protein. In addition, PCE treatment reduced PA-induced reactive oxygen species production and upregulated mRNA levels of antioxidant genes such as nuclear factor (erythroid-derived 2)-like 2 and heme oxygenase 1. Moreover, PCE treatment recovered the expression of autophagy marker genes such as beclin-1 and p62, which was decreased by PA treatment. Treatment with isopsoralen, one of the major components of PCE extract, also recovered the expression of autophagy marker genes and reduced PA-induced apoptosis. In conclusion, PCE exerts protective effects against lipotoxicity via its antioxidant function, and this effect is mediated by activation of autophagy. PCE might be a potential pharmacological agent to protect against neuronal cell injury caused by oxidative stress or lipotoxicity.

Sign in / Sign up

Export Citation Format

Share Document