Islet Encapsulation: Strategies to Enhance Islet Cell Functions

Beck, Jonathan; Angus, Ryan; Madsen, Ben; Britt, David W.; Vernon, Brent L.; Nguyen, Kytai T.

doi:10.1089/ten.2007.13.ft-336

Cited by 41 publications

(65 citation statements)

References 116 publications

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“…In an immune-isolation device, islet cells are at risk from increasing levels of hypoxia and hypoxia-related generation of toxic cytokines and ROS. [1][2][3][4] The bulk of islet cells, consisting of the islet core, are the furthest from the islet surface and furthest from contact with the device's surface and are progressively lost as a function of time in an hypoxic environment, thus contributing to the failure of the islet-containing implant. It is difficult to successfully provide an immune-isolation device with sufficient oxygen to prevent significant islet cell loss.…”

Section: Discussionmentioning

confidence: 99%

“…It is difficult to successfully provide an immune-isolation device with sufficient oxygen to prevent significant islet cell loss. [1][2][3][4][11][12][13][14] Attempts to overcome this problem have included various methods of encapsulation to reduce the diffusion distance from the limiting membrane to the islet, varying the implant site or environment to increase available oxygen, and the inclusion of oxygen binding substances or oxygen producing cells within the …”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14] These methods produced only modest increases in immune-isolated islet survival and function. [1][2][3][4][11][12][13][14] It has been suggested the combination of device design and the modification of islet metabolism may promote the survival of islet cells in a hypoxic environment. 1 It has been reported that islets switch to anaerobic metabolism during exposure to hypoxia, 15 resulting in reduced ATP production and the increased generation of toxic ROS, [15][16][17][18][19][20] contributing to progressive chronic hypoxia-related islet cell death.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

“…Much progress has been made in solving the problems of tissue reactivity to the chemical constituents of immunoisolation devices and the loss of islets housed in the devices from inflammatory and immune rejection processes. [1][2][3][4] However, the loss of islets from prolonged ischemia remains an obstacle to the success of islet immunoisolation as a treatment for diabetes. 1,3,4 Cytoglobin (Cygb) is an intracellular oxygen binding protein found in many mammalian tissues, including islet β-cells.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4] However, the loss of islets from prolonged ischemia remains an obstacle to the success of islet immunoisolation as a treatment for diabetes. 1,3,4 Cytoglobin (Cygb) is an intracellular oxygen binding protein found in many mammalian tissues, including islet β-cells. 5 Cygb may act as an intracellular oxygen scavenger and may provide oxygen to mitochondria as well as cytoplasmic enzymes to inhibit the activation of apoptotic metabolic pathways.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Maintenance of aerobic metabolism increases immunoisolated islet survival

Stagner

Seelan²,

Parthasarathy³

2011

Islets

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Maintenance of aerobic metabolism increases immunoisolated islet survival

Stagner

Seelan²,

Parthasarathy³

2011

Islets

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Stem cell culture engineering – process scale up and beyond

Sharma

Raju

Sui

et al. 2011

Biotechnology Journal

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Advances in stem cell research and recent work on clinical trials employing stem cells have heightened the prospect of stem cell applications in regenerative medicine. The eventual clinical application of stem cells will require transforming cell production from laboratory practices to robust processes. Most stem cell applications will require extensive ex vivo handling of cells, from isolation, cultivation, and directed differentiation to product cell separation, cell derivation, and final formulation. Some applications require large quantities of cells in each defined batch for clinical use in multiple patients; others may be for autologous use and require only small-scale operations. All share a common requirement: the production must be robust and generate cell products of consistent quality. Unlike the established manufacturing process of recombinant protein biologics, stem cell applications will likely see greater variability in their cell source and more fluctuations in product quality. Nevertheless, in devising stem cell-based bioprocesses, much insight could be gained from the manufacturing of biological materials, including recombinant proteins and anti-viral vaccines. The key to process robustness is thus not only the control of traditional process chemical and physical variables, but also the sustenance of cells in the desired potency or differentiation state through controlling non-traditional variables, such as signaling pathway modulators.

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Hemoglobin regulates the metabolic and synthetic function of rat insulinoma cells cultured in a hollow fiber bioreactor

Gundersen

Guo

Powell

et al. 2010

Biotech & Bioengineering

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Pancreatic islet transplantation continues to benefit patients with type 1 diabetes by normalizing glucose metabolism and improving other complications of diabetes. However, islet transplantation therapy is limited by the inadequate availability of pancreatic islets. In order to address this concern, this work investigated the expansion of rat insulinoma cells (INS-1) and their ability to generate insulin in a hollow fiber bioreactor (HFB). The long-term goal of this project is to develop a bioartificial pancreas. HFBs were incubated at two different oxygenation conditions (10% and 19% O(2)) to determine the best scenario for O(2) transport to cultured cells. Also, bovine hemoglobin (BvHb) was supplemented in the cell culture media of the HFBs in order to increase O(2) transport under both oxygenation conditions. Our results show that INS-1 cells expanded under all oxygenation conditions after 2 weeks of culture, with a slightly higher cell expansion under normoxic oxygenation (19% O(2)) for both control HFBs and BvHb HFBs. In addition, cellular insulin production remained steady throughout the study for normoxic control HFBs and BvHb HFBs, while it increased under hypoxic oxygenation (10% O(2)) for both types of HFBs but to different extents. Under the two different oxygenation conditions, cellular insulin production was more uniform with time in BvHb HFBs versus control HFBs. These results, along with qRT-PCR analysis, suggest a possible dysregulation of the insulin-signaling pathway under hypoxic culture conditions. In conclusion, the HFB culture system is an environment capable of expanding insulinomas while maintaining their viability and insulin production capabilities.

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Islet Encapsulation: Strategies to Enhance Islet Cell Functions

Cited by 41 publications

References 116 publications

Maintenance of aerobic metabolism increases immunoisolated islet survival

Maintenance of aerobic metabolism increases immunoisolated islet survival

Stem cell culture engineering – process scale up and beyond

Hemoglobin regulates the metabolic and synthetic function of rat insulinoma cells cultured in a hollow fiber bioreactor

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