Glucose-Insulin Kinetics of the Extravascular Bioartificial Pancreas A Study Using Microencapsulated Rat Islets

Soon‐Shiong, Patrick; Heintz, R; Yao, Zhiwen; Yao, Qiang; Sanford, P. E.; Lanza, Robert; Meredith, Nancy K.

doi:10.1097/00002480-199210000-00021

Cited by 5 publications

(3 citation statements)

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“…For most frequently used peritoneal implantation, it has been demonstrated that the peripheral glucose reflects blood glucose at basal state and during variations of glycemia 66 and that BAP can respond appropriately to an increase in blood glucose concentration, without overshoot hypoglycemia and with a time lag compatible with normal physiologic insulin delivery. [67][68][69][70] For such delivery, including other peripheral sites (and injections), only 10% glucose enters the liver and 56% muscle tissue (liver accessed by the portal vein) and can lead to hyperglycemia and b-cell desensitization. 64 Cherrington noted that "if we want a cure, we will have to deliver insulin portally because only this way glucose is distributed more uniformly: one-third to the liver, one-third to the muscles and one-third elsewhere.…”

Section: Cell Bankingmentioning

confidence: 99%

Bioartificial Pancreas: Materials, Devices, Function, and Limitations

Prokop

2001

Diabetes Technology & Therapeutics

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The term "bioartificial endocrine pancreas" (BEP) was introduced by Anthony Sun in 1980. It was in 1968, however, that Thomas Chang proposed the use of microencapsulated islets as artificial beta-cells. By applying a semipermeable membrane on the top of microcapsules, a system can be produced that is impermeable to viable islet cells and large effector molecules of the immune system, thus providing a protection for transplanted islets against rejection. Since then, the term BEP has not often appeared in papers. Instead, the term "bioartificial pancreas" (BAP) has gained widespread use. In a broader sense, BAP would include an application of suitable endocrine cells and protective polymeric vehicles, but not necessarily providing a filtration barrier of precisely defined properties (e.g., cells injected into a gel of hyaluronate).

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Section: Cell Bankingmentioning

confidence: 99%

Bioartificial Pancreas: Materials, Devices, Function, and Limitations

Prokop

2001

Diabetes Technology & Therapeutics

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“…Levesque et al17 and Sun et al18 have shown that the insulin secretory mechanism and kinetics of the encapsulated islets are similar to those exhibited by free islets. Soon‐Shiong et al19 reported that microcapsulated islets, given sufficient beta‐cell mass, can respond appropriately to an increase in blood glucose concentration, without overshoot hypoglycemia and within a lag lapse compatible with normal physiologic insulin delivery. On the other hand, Schrezenmeir et al20 provided good evidence that islets at various distances from the membrane surface did not have normal patterns of oxygen tension compared to unencapsulated tissue.…”

Section: Microencapsulationmentioning

confidence: 99%

Islet transplantation in the future: Use of a bioartificial pancreas

Maki

1996

J Hep Bil Pancr Surg

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Tight glycemic control effectively delays the onset and slows the progression of diabetic complications in patients with insulin-dependent diabetes mellitus. Successful pancreas transplantation corrects abnormal glucose metabolism but subjects patients to morbidity and mortality associated with chronic immunosuppression. Immune exclusion devices containing pancreatic islets (bioartificial pancreas devices) are designed to provide glycemic control through islet transplantation without immunosuppression. The immune exclusion is achieved by separating allogeneic or xenogeneic islets from the host by semipermeable membranes that allow only small molecules, such as glucose, insulin, and nutrients, to pass through. Immune lymphocytes and immunoglobulins are excluded by the membrane and are unable to cause destruction of the islets. This report provides a b~ief review of three types of bioartificial pancreas devices used for the treatment of diabetes, i.e., perfusion-based vascular devices, diffusionbased chambers and microcapsules, and describes recent progress in each area.

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“…2 Microcapsule membranes have been shown to protect the graft against immune cells, 3,4 antibodies, 5 and complement proteins. 6 How-ever, reproducibly successful results have not been reported and graft failure is always associated with a host reaction that eventually develops around implanted microcapsules. [7][8][9][10][11] This host reaction to microcapsule (HRM) is similar to a foreign body reaction to biomaterials because a pericapsular fibrosis reaction develops around unseeded as well as islet bearing microcapsules.…”

Section: Introductionmentioning

confidence: 99%

Time course of transforming growth factor-?1 (TGF-?1) mRNA expression in the host reaction to alginate-poly-L-lysine microcapsules following implantations into rat epididymal fat pads

Robitaille

Desbiens

Henley

et al. 2000

J. Biomed. Mater. Res.

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Microencapsulation of islets of Langerhans within semipermeable membranes has been proposed to prevent their immune destruction after transplantation. However, the successful application of this method is impaired by a pericapsular reaction, which eventually induces graft failure. Our goal is to study the role of cytokines in the pathogenesis of this reaction, using the model of alginate-poly-L-lysine microcapsule implantation into Wistar rat epididymal fat pads (EFP). The specific objective of this study was to determine the time course of transforming growth factor (TGF)-beta(1) mRNA expression by semi-quantitative reverse transcriptase-polymerase chain reaction. Microcapsules induced an increase of TGF-beta(1) mRNA expression that reached a maximum 14 days after implantation. Seven, 14, 30, and 60 days after microcapsule implantation, the expression of TGF-beta(1) mRNA was significantly higher in pericapsular infiltrate cells than in nonimplanted EFP cells (p<0.05, p<0.0001, p<0.005, and p<0.01, respectively). Injection of physiological saline induced a small and gradual augmentation of TGF-beta(1) mRNA expression with a maximum 30 days after injection (p<0.01 vs. nonimplanted EFP cells). These results demonstrated that microcapsule implantation, in comparison with saline injection, induce an early, extended, and amplified TGF-beta(1) mRNA expression. This suggests that TGF-beta(1) plays a role in the pathogenesis of the pericapsular host reaction.

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Glucose-Insulin Kinetics of the Extravascular Bioartificial Pancreas A Study Using Microencapsulated Rat Islets

Cited by 5 publications

References 0 publications

Bioartificial Pancreas: Materials, Devices, Function, and Limitations

Bioartificial Pancreas: Materials, Devices, Function, and Limitations

Islet transplantation in the future: Use of a bioartificial pancreas

Time course of transforming growth factor-?1 (TGF-?1) mRNA expression in the host reaction to alginate-poly-L-lysine microcapsules following implantations into rat epididymal fat pads

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