The cytoprotection of chitosan based hydrogels in xenogeneic islet transplantation: An in vivo study in streptozotocin-induced diabetic mouse

Yang, Kai Chiang; Qi, Zhi; Wu, Chang Chin; Shirouza, Yasumasa; Lin, Feng Huei; Yanai, Goichi; Sumi, Shoichiro

doi:10.1016/j.bbrc.2010.02.089

Cited by 42 publications

(23 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data demonstrated that IDO expression induced in islets by lipofection improved metabolic control of streptozotocindiabetic rodents and prolonged allograft survival (10) . The cytoprotection of chitosan hydrogels in xenogeneic islet transplantation was demonstrated by Yang et al (61) . It has showed that islets encapsulated in chitosan hydrogels secreted insulin in response to the glucose stimulation as naked islets with higher cell survival.…”

Section: Discussionmentioning

confidence: 96%

Islet transplantation in rodents: do encapsulated islets really work?

Souza

Chaib

Lacerda

et al. 2011

Arq. Gastroenterol.

View full text Add to dashboard Cite

-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.

show abstract

Section: Discussionmentioning

confidence: 96%

Islet transplantation in rodents: do encapsulated islets really work?

Souza

Chaib

Lacerda

et al. 2011

Arq. Gastroenterol.

View full text Add to dashboard Cite

show abstract

“…For isolation of rat islets, Lewis or Wistar rats (male, aged 9-11 wk, Shimizu Laboratory Supplies) were used. Islet isolation was performed according to previously described methods (25). Briefly, through midline laparotomy, 10 mL of a type XI collagenase solution (1200 CDU/mL, C9407, Sigma-Aldrich) was infused into the common bile duct that was ligated at the hepatic side before the inflow into the duodenum.…”

Section: Isolation Of Rat and Mouse Primary Islets And Preparation Ofmentioning

confidence: 99%

PHLDA3 is a novel tumor suppressor of pancreatic neuroendocrine tumors

Ohki¹,

Saito

Chen

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

122

View full text Add to dashboard Cite

The molecular mechanisms underlying the development of pancreatic neuroendocrine tumors (PanNETs) have not been well defined. We report here that the genomic region of the PHLDA3 gene undergoes loss of heterozygosity (LOH) at a remarkably high frequency in human PanNETs, and this genetic change is correlated with disease progression and poor prognosis. We also show that the PHLDA3 locus undergoes methylation in addition to LOH, suggesting that a two-hit inactivation of the PHLDA3 gene is required for PanNET development. We demonstrate that PHLDA3 represses Akt activity and Akt-regulated biological processes in pancreatic endocrine tissues, and that PHLDA3-deficient mice develop islet hyperplasia. In addition, we show that the tumor-suppressing pathway mediated by MEN1, a well-known tumor suppressor of PanNETs, is dependent on the pathway mediated by PHLDA3, and inactivation of PHLDA3 and MEN1 cooperatively contribute to PanNET development. Collectively, these results indicate the existence of a novel PHLDA3-mediated pathway of tumor suppression that is important in the development of PanNETs.p53 | PH domain | everolimus | p53 target gene | mTOR N euroendocrine tumors (NETs) arise from cells of the endocrine and nervous systems, and are found in tissues such as lung, pancreas and pituitary (1-3). NETs often produce, store and release biogenic amines and polypeptide hormones, and secretary granules containing these products provide a diagnostic marker for NETs. The mechanisms underlying the development of NETs remain unclear to date, due to the low incidence of these tumors and due to the lack of suitable experimental model systems, including genetically engineered mouse models. Pancreatic NET (PanNET), which is probably the best-studied NET, is the second-most common pancreatic tumor, having an incidence of ∼1 per 100,000 individuals. Patients having late-stage PanNET often harbor tumors that are unresectable or metastatic and face limited treatment options. Accordingly, the prognosis of patients having metastatic PanNET is the worst among the NET subtypes, with a 5-y survival rate of 27-43% (1). Recently, the drug Everolimus has shown promise in the treatment of PanNETs (4), providing a significant improvement in progression-free survival. Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a downstream mediator of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. The striking efficacy of Everolimus demonstrates the importance of the PI3K/Akt pathway in the pathology of PanNETs.In agreement with these clinical results, studies on pancreatic endocrine cell lines have identified the PI3K/Akt signaling pathway as a major proliferation and survival pathway in these cells (5). Activated Akt phosphorylates substrates such as mTOR and controls various biological processes, including protein synthesis, proliferation, cell growth, and survival. Regulation of pancreatic islet β-cell proliferation, cell size, and apoptosis by Akt has been demonstrated using various mouse models. For examp...

show abstract

“…Besides alginates, other materials have also been studied for microencapsulation, including sol-gel silica (SiO 2 )(134, 135), polyacrylates(136), agarose(137, 138), chitosan(139). ..…”

Section: Immunoisolation Of Transplanted Islets: Different Approachesmentioning

confidence: 99%

Membranes to achieve immunoprotection of transplanted islets

2014

View full text Add to dashboard Cite

Transplantation of islet or beta cells is seen as the cure for type 1 diabetes since it allows physiological regulation of blood glucose levels without requiring any compliance from the patients. In order to circumvent the use of immunosuppressive drugs (and their side effects), semipermeable membranes have been developed to encapsulate and immunoprotect transplanted cells. This review presents the historical developments of immunoisolation and provides an update on the current research in this field. A particular emphasis is laid on the fabrication, characterization and performance of membranes developed for immunoisolation applications.

show abstract

The cytoprotection of chitosan based hydrogels in xenogeneic islet transplantation: An in vivo study in streptozotocin-induced diabetic mouse

Cited by 42 publications

References 24 publications

Islet transplantation in rodents: do encapsulated islets really work?

Islet transplantation in rodents: do encapsulated islets really work?

PHLDA3 is a novel tumor suppressor of pancreatic neuroendocrine tumors

Membranes to achieve immunoprotection of transplanted islets

Contact Info

Product

Resources

About