Endothelial Progenitor Cells Enhance Islet Engraftment, Influence b-Cell Function, and Modulate Islet Connexin 36 Expression

This article has been made available by the publisher under a Creative Commons Attribution Non-Commercial (CC BY NC) license. https://www.cognizantcommunication.com/general-subscription-policies/open-access-policy Accessed 10/2/15The success of pancreatic islet transplantation is limited by delayed engraftment and suboptimal function in the longer term. Endothelial progenitor cells (EPCs) represent a potential cellular therapy that may improve the engraftment of transplanted pancreatic islets. In addition, EPCs may directly affect the function of pancreatic β-cells. The objective of this study was to examine the ability of EPCs to enhance pancreatic islet transplantation in a murine syngeneic marginal mass transplant model and to examine the mechanisms through which this occurs. We found that cotransplanted EPCs improved the cure rate and initial glycemic control of transplanted islets. Gene expression data indicate that EPCs, or their soluble products, modulate the expression of the β-cell surface molecule connexin 36 and affect glucose-stimulated insulin release in vitro. In conclusion, EPCs are a promising candidate for improving outcomes in islet transplantation, and their mechanisms of action warrant further study

Insulin-like growth factor-II (IGF-II) prevents proinflammatory cytokine-induced apoptosis and significantly improves islet survival after transplantation

BackgroundThe early loss of functional islet mass (50-70%) due to apoptosis after clinical transplantation contributes to islet allograft failure. Insulin-like growth factor (IGF)-II is an antiapoptotic protein that is highly expressed in β-cells during development but rapidly decreases in postnatal life.MethodsWe used an adenoviral (Ad) vector to overexpress IGF-II in isolated rat islets and investigated its antiapoptotic action against exogenous cytokines interleukin-1β- and interferon-γ-induced islet cell death in vitro. Using an immunocompromised marginal mass islet transplant model, the ability of Ad-IGF-II-transduced rat islets to restore euglycemia in nonobese diabetic/severe combined immunodeficient diabetic recipients was assessed.ResultsAd-IGF-II transduction did not affect islet viability or function. Ad-IGF-II cytokine-treated islets exhibited decreased cell death (40% ± 2.8%) versus Ad-GFP and untransduced control islets (63.2% ± 2.5% and 53.6% ± 2.3%, respectively). Ad-IGF-II overexpression during cytokine treatment resulted in a marked reduction in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive apoptotic cells (8.3% ± 1.4%) versus Ad-GFP control (41% ± 4.2%) and untransduced control islets (46.5% ± 6.2%). Western blot analysis confirmed that IGF-II inhibits apoptosis via activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. Transplantation of IGF-II overexpressing islets under the kidney capsule of diabetic mice restored euglycemia in 77.8% of recipients compared with 18.2% and 47.5% of Ad-GFP and untransduced control islet recipients, respectively (PConclusionsAntiapoptotic IGF-II decreases apoptosis in vitro and significantly improved islet transplant outcomes in vivo. Antiapoptotic gene transfer is a potentially powerful tool to improve islet survival after transplantation.Hughes, Amy; Mohanasundaram, Daisy; Kireta, Svjetlana; Jessup, Claire F.; Drogemuller, Chris J.; Coates, P. Toby H

Australia and New Zealand Islet and Pancreas Transplant Registry Annual Report 2018—Islet Donations, Islet Isolations, and Islet Transplants

Background. This is an excerpt from chapter 4 of the annual registry report from the Australia and New Zealand islet and pan- creas transplant registry. The full report is available at http://anziptr.org/reports/. Methods. We report data for all allogeneic islet isolation and transplant activity from 2002 to end 2017. Solid organ pancreas transplantation activity is reported separately. New Zealand does not have an islet transplant program. Data analysis was performed using Stata software version 14 (StataCorp, College Station, TX). Results. From 2002 to 2017, a total of 104 allogeneic islet transplants were performed in 62 recipients. Conclusions. The number of islet transplants performed in Australia was slightly lower in 2017 but continues to increase over time

Zinc and Zinc Transporter Regulation in Pancreatic Islets and the Potential Role of Zinc in Islet Transplantation

The critical trace element zinc is essential for normal insulin production, and plays a central role in cellular protection against apoptosis and oxidative stress. The regulation of zinc within the pancreas and β-cells is controlled by the zinc transporter families ZnT and ZIP. Pancreatic islets display wide variability in the occurrence of these molecules. The zinc transporter, ZnT8 is an important target for autoimmunity in type 1 diabetes. Gene polymorphisms of this transporter confer sensitivity for immunosuppressive drugs used in islet transplantation. Understanding the biology of zinc transport within pancreatic islets will provide insight into the mechanisms of β-cell death, and may well reveal new pathways for improvement of diabetes therapy, including islet transplantation. This review discusses the possible roles of zinc in β-cell physiology with a special focus on islet transplantation

Australia and New Zealand Islet and Pancreas Transplant Registry Annual Report 2018—Islet Donations, Islet Isolations, and Islet Transplants

Background. This is an excerpt from chapter 4 of the annual registry report from the Australia and New Zealand islet and pancreas transplant registry. The full report is available at http://anziptr.org/reports/. Methods. We report data for all allogeneic islet isolation and transplant activity from 2002 to end 2017. Solid organ pancreas transplantation activity is reported separately. New Zealand does not have an islet transplant program. Data analysis was performed using Stata software version 14 (StataCorp, College Station, TX). Results. From 2002 to 2017, a total of 104 allogeneic islet transplants were performed in 62 recipients. Conclusions. The number of islet transplants performed in Australia was slightly lower in 2017 but continues to increase over time