Elevation of vascular endothelial growth factor production and its effect on revascularization and function of graft islets in diabetic rats

Cheng, Ying; Liu, Yongfeng; Zhang, Jialin; Li, Tie-Min; Zhao, Ning

doi:10.3748/wjg.v13.i20.2862

Cited by 47 publications

(27 citation statements)

References 25 publications

(24 reference statements)

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“…Nonencapsulated islets may be injected into the liver (4,16,18,19,35,44,50,52) , kidney (5,14,15,16,17,24,27,28,32,34,35,42,46,47) , peritoneal cavity (11,35) , bone marrow (41) and subcutaneous tissue (22,48) . Ikebukuro et al (19) showed that islets and bone marrow cells, when injected into the liver using irradiation as immunosuppression, can increase the functionality of the cells for more than 365 days.…”

Section: Discussionmentioning

confidence: 99%

“…Trying to increase the blood supply of the graft soon after implantation, Cheng et al (5) have injected vascular endothelial cells L and vascular endothelial growth factor (VEGF) to stimulate angiogenesis. The use of growth factors was made of in other works too (5,33,62) .…”

Section: Discussionmentioning

confidence: 99%

“…The use of growth factors was made of in other works too (5,33,62) . They saw that in chronically isquemic tissues these factors where decreased and that premature islet revascularization could improve the outcome of islet transplantation and enhance the graft survival.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Islet transplantation in rodents: do encapsulated islets really work?

Souza

Chaib

Lacerda

et al. 2011

Arq. Gastroenterol.

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-Context -Diabetes mellitus type I affects around 240 million people in the world and only in the USA 7.8% of the population.It has been estimated that the costs of its complications account for 5% to 10% of the total healthcare spending around the world. According to World Health Organization, 300 million people are expected to develop diabetes mellitus by the year 2025. The pancreatic islet transplantation is expected to be less invasive than a pancreas transplant, which is currently the most commonly used approach. Objectives -To compare the encapsulated and free islet transplantation in rodents looking at sites of islet implantation, number of injected islets, viability and immunosuppression. Methods -A literature search was conducted using MEDLINE/PUBMED and SCIELO with terms about islet transplantation in the rodent from 2000 to 2010. We found 2,636 articles but only 56 articles from 2000 to 2010 were selected. Results -In these 56 articles used, 34% were encapsulated and 66% were nonencapsulated islets. Analyzing both types of islets transplantation, the majority of the encapsulated islets were implanted into the peritoneal cavity and the nonencapsulated islets into the liver, through the portal vein. In addition, the great advantage of the peritoneal cavity as the site of islet transplantation is its blood supply. Both vascular endothelial cells and vascular endothelial growth factor were used to stimulate angiogenesis of the islet grafts, increasing the vascularization rapidly after implantation. It also has been proven that there is influence of the capsules, since the larger the capsule more chances there are of central necrosis. In some articles, the use of immunosuppression demonstrated to increase the life expectancy of the graft. Conclusion -While significant progress has been made in the islets transplantation field, many obstacles remain to be overcome. Microencapsulation provides a means to transplant islets without immunosuppressive agents and may enable the performance of xenotransplantation. The use of alternative donor sources, fewer islets per capsule and the appropriate deployment location, such as the peritoneal cavity, may give a future perspective to the application of immunoprotective capsules and viability in clinical practice. A variety of strategies, such as genetic engineering, co-encapsulation, improvement in oxygen supply or the establishment of hypoxia resistance will also improve the islet transplantation performance. It remains to be determined which combination of strategies with encapsulation can fulfill the promise of establishing a simple and safe transplantation as a cure for diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Islet transplantation in rodents: do encapsulated islets really work?

Souza

Chaib

Lacerda

et al. 2011

Arq. Gastroenterol.

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show abstract

“…Studies found that CTGF can induce the production of basement membrane components, such as collagen and fibronectin cularization and maintaining the vascular permeability of the rat grafted islets [68]. Upregulation of VEGF accelerates islet revascularization, which increases the survival of transplanted islets [69]. Experiments have shown that VEGF knocked-out mice contain defective remaining capillaries.…”

Section: Connective Tissue Growth Factormentioning

confidence: 99%

The endocrine role between β cells and intra-islet endothelial cells [Review]

Cao

Wang

2014

Endocr J

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Abstract. The islets of Langerhans is the endocrine function region of pancreas, which exist in five cell types. The majority of endocrine cells are insulin-secreting β cells, mixed up with glucagon-secreting α-cells. The islets of Langerhans are highly vascularized, and the capillary network around the islet is about five times denser than that in the exocrine tissues. It guarantees endocrine cells adequately contact with the capillary networks. Above mentioned is the basis of deep study the interaction between β cells and capillary. Increasing number of studies contribute to the consensus that endothelial cells have positive effects in the islet microenvironment. Endothelial cells can act as endocrine cells which release many active substances, such as hepatocyte growth factors (HGF), thrombospondin-1(TSP-1), laminins, and collagens by means of different molecule pathways, inducing β cells differentiation, proliferation, survivor, and insulin release next to the vessels. Apart from the effect of endothelial cells on β cells by paracrine fashion, the islets can utilize VEGF-A, angiopoietin-1 and insulin signaling to increase the interaction with endothelial cells. As the endocrine role of endothelial cells to β cells, it may be a novel target to stimulate β cells regeneration, promote vascularization post islet transplantation strategy in the treatment of diabetes mellitus.

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“…Such approaches are expected to ensure adequate microvascular perfusion to islet cells and protect implanted islet cells from hypoxia-induced inflammation and necrosis, which will ultimately improve the outcome of islet transplantation by reducing the donor/recipient ratio thus increasing the success rate of islet transplantation [28]. Antioxidant supplementation [29,68], elevation of vascular endothelial growth factor (VEGF) delivery [30] to islet grafts and co-transplantation of bone marrow-derived mesenchymal stem cells [31] improves the outcome of islet transplantation by enhancing islet revascularization.…”

Section: Islet Transplantationmentioning

confidence: 99%

Diabetes Mellitus: New Challenges and Innovative Therapies

Sena¹,

Bento²,

Pereira³

et al. 2013

New Strategies to Advance Pre/Diabetes Care: Integrative Approach by PPPM

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Diabetes mellitus is a widespread disease prevalence and incidence of which increases worldwide. The introduction of insulin therapy represented a major breakthrough in type 1 diabetes; however, frequent hyper-and hypoglycemia seriously affects the quality of life of these patients. New therapeutic approaches, such as whole pancreas transplant or pancreatic islet transplant, stem cell, gene therapy and islets encapsulation are discussed in this review. Regarding type 2 diabetes, therapy has been based on drugs that stimulate insulin secretion (sulphonylureas and rapid-acting secretagogues), reduce hepatic glucose production (biguanides), delay digestion and absorption of intestinal carbohydrate (alpha-glucosidase inhibitors) or improve insulin action (thiazolidinediones). This review is also focused on the newer therapeutically approaches such as incretin-based therapies, bariatric surgery, stem cells and other emerging therapies that promise to further extend the options available. Gene-based therapies are among the most promising emerging alternatives to conventional treatments. Some of these therapies rely on genetic modification of non-differentiated cells to express pancreatic endocrine developmental factors, promoting differentiation of nonendocrine cells into β-cells, enabling synthesis and secretion of insulin in a glucose-regulated manner. Alternative therapies based on gene silencing using vector systems to deliver interference RNA to cells (i.e. against VEGF in diabetic retinopathy) are also a promising therapeutic option for the treatment of several diabetic complications. In conclusion, treatment of diabetes faces now a new era that is characterized by a variety of innovative therapeutic approaches that will improve quality-life and allow personalized therapyplanning in the near future.

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Elevation of vascular endothelial growth factor production and its effect on revascularization and function of graft islets in diabetic rats

Abstract: AIM:To determine whether the elevated vascular endothelial growth factor (VEGF) expression produced by the transfected vascular endothelial cells (VECs) could stimulate angiogenesis of the graft islets and exert its effect on the graft function.

Cited by 47 publications

References 25 publications

Islet transplantation in rodents: do encapsulated islets really work?

Islet transplantation in rodents: do encapsulated islets really work?

The endocrine role between β cells and intra-islet endothelial cells [Review]

Diabetes Mellitus: New Challenges and Innovative Therapies

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