Treatment of Severe Diabetes Mellitus for More Than One Year Using a Vascularized Hybrid Artificial Pancreas

Maki, Takashi; Lodge, J.P.A.; Carretta, Mauro; Ohzato, Hiroki; Borland, Kermit; Sullivan, S John; Staruk, J E; Muller, Thomas E.; Solomon, Barry A.; Chick, William L.

doi:10.1097/00007890-199304000-00005

Cited by 60 publications

(44 citation statements)

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“…These devices permit close contact between the bloodstream and the islets, leading to efficient diffusional transport of metabolites. Encapsulation of islets in this device has been shown to induce normoglycemia in various animal models of diabetes including rats, dogs, and monkeys (Sun et al, 1977;Maki et al, 1993). The use of this device, however, requires intense systemic anticoagulation because of the direct contact of foreign material with blood and the potential for blood clotting, leading to potentially fatal thrombus formation, which is indicative of low biocompatibility of the implant material.…”

Section: A Immunoisolation Of Transplanted Isletsmentioning

confidence: 99%

Biological and Biomaterial Approaches for Improved Islet Transplantation

2006

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Section: A Immunoisolation Of Transplanted Isletsmentioning

confidence: 99%

Biological and Biomaterial Approaches for Improved Islet Transplantation

2006

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“…It is technically advanced and has been tested extensively in small [9] as well as in large animals [9,10]. The original device was composed of a number of small diameter artificial capillaries contained by one large diameter tube.…”

Section: Macroencapsulation Of Pancreatic Isletsmentioning

confidence: 99%

“…The design allows close contact between the islets and blood which are separated only by the microporous walls of the capillaries. These devices were found to induce normoglycaemia in diabetic rats [9], dogs [10] and monkeys [9] but required systemic anticoagulation. The duration of this normoglycaemia was usually restricted to several hours and successes of a somewhat longer duration were exceptional.…”

Section: Macroencapsulation Of Pancreatic Isletsmentioning

confidence: 99%

Considerations for successful transplantation of encapsulated pancreatic islets

2002

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A major challenge in the treatment of Type I (insulindependent) diabetes mellitus is the prevention of late complications, and thereby improvement of the quality of patient life. There is no dispute that euglycaemia is of essential importance to reach that goal. Euglycaemia can be achieved by insulin treatment and the results of the Diabetes control and complications trial clearly show that insulin treatment delays the onset and reduces the progression of diabetic complications [1]. Intensified treatment, however, is not a simple chore because it requires multiple daily injections, frequent monitoring, dosage adaptations and, thus, patient compliance. It is also associated with frequent episodes of severe hypoglycaemia and with glycaemic unawareness. A different approach to euglycaemia is to provide the diabetic patient with an endogenous rather than an exogenous source of insulin by the transplantation of the endocrine pancreatic tissue. Pancreatic organ transplantation is now an es- Diabetologia (2002) AbstractEncapsulation of pancreatic islets allows for transplantion in the absence of immunosuppression. The technology is based on the principle that transplanted tissue is protected for the host immune system by an artificial membrane. Encapsulation offers a solution to the shortage of donors in clinical islet transplantation because it allows animal islets or insulin-producing cells engineered from stem cells to be used. During the past two decades three major approaches to encapsulation have been studied. These include intravascular macrocapsules, which are anastomosed to the vascular system as AV shunt; extravascular macrocapsules, which are mostly diffusion chambers transplanted at different sites; and extravascular microcapsules transplanted in the peritoneal cavity. The advantages and pitfalls of these three approaches are discussed and compared in the light of their applicability to clinical islet transplantation. All systems have been shown to be successful in preclinical studies but not all approaches meet the technical or physiological requirements for application in human beings. The extravascular approach has advantages over the intravascular because since it is associated with less complications such as thrombosis and infection. Microcapsules, due to their spatial characteristics, have a better diffusion capacity than macrocapsules. Recent progress in biocompatibility of microcapsules has brought this technology close to clinical application. Critical issues such as limitations in the functional performance and survival are being discussed. The latest results show that both issues can be solved by the transplantation of microencapsulated islets close to blood vessels in prevascularized solid supports. [Diabetologia (2002) 45: 159±173]

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“…Suboptimal nutrient and oxygen diffusion across the layers leading to reduced islet viability, poor graft function, and ultimately graft failure, limit the ability of these devices to achieve prolonged insulin independence. Despite these disadvantages, the ease with which they can be retrieved after implantation, for evaluation of cell viability [62] and function [63,64] has led to several biomaterial device engineers to prefer this conformation over all others. This includes the Sernova Cell Pouch TM ( Sernova Corp, Canada), the VC-01 TM device (Viacyte LLC, San Diego, CA) and the Theracyte device (Theracyte, Laguna Hills, CA) some of which can even be modified to promote vascularization while simultaneously providing effective immunoisolation [65,66].…”

Section: Planar Devicesmentioning

confidence: 99%