Clinical islet transplantation

Kaufman, Dixon B.; Lowe, William L.

doi:10.1007/s11892-003-0028-7

Cited by 11 publications

(7 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Islet transplantation has proven to be an effective treatment in a select population of individuals with type 1 diabetes, but many obstacles remain before it can be more broadly applied. The need for a large number of islets to achieve euglycemia and the progressive deterioration in islet function over time represent two significant barriers (3,25). The cause of these problems is not yet fully elucidated but can not be fully accounted for by allo-or autoimmune-mediated damage to the islets (3).…”

Section: Discussionmentioning

confidence: 99%

Polymer Scaffolds as Synthetic Microenvironments for Extrahepatic Islet Transplantation

et al. 2006

Self Cite

View full text Add to dashboard Cite

These findings indicate that a synthetic polymer scaffold can serve as a platform for islet transplantation and improves the function of extrahepatically transplanted islets compared to islets transplanted without a scaffold. The scaffold may also be useful to deliver bioactive molecules to modify the microenvironment surrounding the transplanted islets and, thus, enhance islet survival and function.

show abstract

Section: Discussionmentioning

confidence: 99%

Polymer Scaffolds as Synthetic Microenvironments for Extrahepatic Islet Transplantation

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…Islet transplantation has proven to be a viable option for the treatment of people with type 1 diabetes, but the shortage of human cadaveric pancreata and deleterious consequences of long‐term immunosuppression limit the of number of patients that can be treated to a small fraction of the diabetic population . Xenotransplantation of porcine islets is a promising alternative for human islets, as pigs are an abundant source of pancreata, pigs and humans have similar blood glucose levels, and porcine insulin differs from human insulin by only one amino acid.…”

Section: Introductionmentioning

confidence: 99%

The effect of hypoxia on free and encapsulated adult porcine islets—an in vitro study

Muthyala

Safley

Gordan

et al. 2016

Xenotransplantation

View full text Add to dashboard Cite

Background Adult porcine islets (APIs) constitute a promising alternative to human islets in treating Type 1 diabetes. The intrahepatic site has been used in pre-clinical primate studies of API xenografts; however, an estimated two-thirds of donor islets are destroyed after intraportal infusion due to a number of factors, including the instant blood mediated inflammatory reaction (IBMIR), immunosuppressant toxicity, and poor reestablishment of extracellular matrix connections. Intraperitoneal (i.p.) transplantation of non-vascularized encapsulated islets offers several advantages over intrahepatic transplantation of free islets, including avoidance of IBMIR, immunoprotection, accommodation of a larger graft volume, and reduced risk of hemorrhage. However, there exists evidence that the peritoneal site is hypoxic, which likely impedes islet function. Methods We tested the effect of hypoxia (2-5% oxygen or pO2: 15.2-38.0 mmHg) on free and encapsulated APIs over a period of 6 days in culture. Free and encapsulated APIs under normoxia served as controls. Islet viability was evaluated with a viability/cytotoxicity assay using calcein AM and ethidium bromide on days 1, 3 and 6 of culture. Alamar blue assay was used to measure the metabolic activity on days 1 and 6. Insulin in spent medium was assayed by ELISA on days 1 and 6. Results Viability staining indicated that free islet clusters lost their integrity and underwent severe necrosis under hypoxia; encapsulated islets remained intact, even when they began to undergo necrosis. Under hypoxia, thae metabolic activity and insulin secretion (normalized to metabolic activity) of both free and encapsulated islets decreased relative to islets cultured under normoxic conditions. Conclusions Hypoxia (2-5% oxygen or pO2: 15.2-38.0 mmHg) affects the viability, metabolic activity and insulin secretion of both free and encapsulated APIs over a 6-day culture period. Encapsulation augments islet integrity under hypoxia, but it does not prevent loss of viability, metabolic activity, or insulin secretion.

show abstract

“…Recent improvement in the success of transplanting pancreatic islets of Langerhans for treatment of type 1 diabetes in humans (Shapiro et al, 2000;Kaufman and Lowe, 2003;Lakey et al, 2003;Sutherland, 2003;Hering et al, 2004;Hering 2005;Ricordi et al, 2005) has prompted interest for more widespread application, which will require standardized islet quality assessment methods to ensure in vivo efficacy (Knazek, 2002;Weber et al, 2002), particularly because islets are compromised during the steps from pancreas procurement to transplantation. Human organs are procured from brain dead donors (Bretzel et al, 1994;Contreras et al, 2003) and are exposed to periods of warm and cold ischemia (Papas et al, 2005;Paraskevas et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

A stirred microchamber for oxygen consumption rate measurements with pancreatic islets

Papas

Pisania

et al. 2007

Biotech & Bioengineering

102

106

View full text Add to dashboard Cite

Improvements in pancreatic islet transplantation for treatment of diabetes are hindered by the absence of meaningful islet quality assessment methods. Oxygen consumption rate (OCR) has previously been used to assess the quality of organs and primary tissue for transplantation. In this study, we describe and characterize a stirred microchamber for measuring OCR with small quantities of islets. The device has a titanium body with a chamber volume of about 200 µL and is magnetically stirred and water jacketed for temperature control. Oxygen partial pressure (pO 2 ) is measured by fluorescence quenching with a fiber optic probe, and OCR is determined from the linear decrease of pO 2 with time. We demonstrate that measurements can be made rapidly and with high precision. Measurements with βTC3 cells and islets show that OCR is directly proportional to the number of viable cells in mixtures of live and dead cells and correlate linearly with membrane integrity measurements made with cells that have been cultured for 24 h under various stressful conditions.

show abstract

Clinical islet transplantation

Cited by 11 publications

References 69 publications

Polymer Scaffolds as Synthetic Microenvironments for Extrahepatic Islet Transplantation

Polymer Scaffolds as Synthetic Microenvironments for Extrahepatic Islet Transplantation

The effect of hypoxia on free and encapsulated adult porcine islets—an in vitro study

A stirred microchamber for oxygen consumption rate measurements with pancreatic islets

Contact Info

Product

Resources

About