The Efficacy of Intraperitoneal Pancreatic Islet Isografts in the Reversal of Diabetes in Rats

Fritschy, Wilbert M.; Straaten, Jeanette F.M. van; Vos, Paul de; Strubbe, J.H.; Wolters, G. H. J.; Schilfgaarde, R. van

doi:10.1097/00007890-199111000-00004

Cited by 59 publications

(41 citation statements)

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“…Even the mice with syngeneic islets in the peritoneal cavity became lighter than the control mice. Similar limitation in weight gain compared with controls was observed in rats transplanted with microencapsulated or naked islets [12,33]. It is also possible that the presence of substantial volume of capsules in peritoneal cavity led to a loss in appetite.…”

Section: Discussionmentioning

confidence: 54%

C-Peptide responses after meal challenge in mice transplanted with microencapsulated rat islets

et al. 2001

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For transplantation of pancreatic islets into patients with Type 1 (insulin-dependent) diabetes mellitus, microencapsulation could provide protection against immune destruction. Such protection has been demonstrated in several animal models, in which random glucose concentrations have been maintained in the normal range for extended periods of time: in rodents [1±8], dogs [9,10], or cynomologus monkeys [11]. At present, it has only been proved practical to place microcapsules into the peritoneal cavity but it is not clear if this site allows adequate exchange of nutrients, metabolites and insulin between the encapsulated islets and the systemic circulation. To our knowledge, there are few studies of glucose regulation by transplanted microencapsulated islets and these mostly describe only glucose concentrations without providing information about corresponding insulin Diabetologia (2001) Abstract Aims/hypothesis. This study aimed to assess a response of microencapsulated rat islets to a meal challenge after being transplanted intraperitoneally into diabetic mice. Methods. Microencapsulated rat islets or control naked syngeneic mouse islets were transplanted intraperitoneally into mice with streptozotocin-induced diabetes. Meal challenges were done 3, 6 and 9 weeks after transplantation. Glucose-induced insulin secretion from microencapsulated islets before and after transplantation was assessed in vitro.Results. Within the first week, all animals transplanted with either microencapsulated rat islets or with syngeneic murine islets became normoglycaemic ( < 11 mmol/l). At 4 and 6 weeks, body weight was less than normal in the non-diabetic control mice. Mice with the encapsulated rat islets had lower fasting glucose concentrations and more rapid glucose clearance after a meal challenge than the control mice. The group of mice with transplanted syngeneic islets had similar glucose profiles to control mice, except for slightly accelerated glucose clearance. The C peptide responses of mice with either microencapsulated or naked islets were clearly lower than the controls. An increase of C peptide appeared as early as 20 min in the plasma of the group with encapsulated islets, but this was considerably slower than in the other two groups. Microencapsulated rat islets retrieved 9 weeks after transplantation did not lose their ability to respond to glucose, but their output was less than half of the pretransplant control islets. Conclusion/interpretation. The delivery of C peptide and presumably the accompanying insulin are delayed by restrictions of the capsules and the peritoneal location. However, this delay in reaching peripheral target organs does not prevent microencapsulated grafts from efficiently clearing glucose after a meal. [Diabetologia (2001) 44: 646±653]

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Section: Discussionmentioning

confidence: 54%

C-Peptide responses after meal challenge in mice transplanted with microencapsulated rat islets

et al. 2001

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“…Graft failure could not be explained either by fibrotic overgrowth and subsequent cell death because this was observed in only a small minority of capsules as described above. It could also not have been caused by insufficient viability of isolated islets because isogenically transplanted naked, non-encapsulated islets survived after intraperitoneal implantation [96].…”

Section: Functional Performance Of Microencapsulated Islet Graftsmentioning

confidence: 99%

“…One potential explanation of that phenomenon is that the peritoneal cavity is known to be less accommodating to transplanted islets. It has been shown that naked syngeneic islets transplanted under the kidney capsule or into the portal vein of diabetic rats were much more efficient in normalising glucose concentrations than when transplanted into the peritoneal cavity [96,98,99]. Additionally, islets in microcapsules in the absence of the vascularization of a graft, could be exposed to relative hypoxia [11,100].…”

Section: Functional Performance Of Microencapsulated Islet Graftsmentioning

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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“…As islets differ considerably in size [3,4], seemingly similar graft sizes, when defined by the nmnber of transplanted islets, may well represent a considerable difference in the actual number of Beta cells of the islet grafts. In addition, the differing results between the transplant sites have been attributed to efficacy of engraftment after islet transplantation [5] and to the route of venous drainage of insulin by the endocrine graft, i. e. to the portal or to the systemic circulation [6][7][8].…”

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confidence: 99%

Insulin secretion by rat islet isografts of a defined endocrine volume after transplantation to three different sites

et al. 1992

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The Efficacy of Intraperitoneal Pancreatic Islet Isografts in the Reversal of Diabetes in Rats

Cited by 59 publications

References 0 publications

C-Peptide responses after meal challenge in mice transplanted with microencapsulated rat islets

C-Peptide responses after meal challenge in mice transplanted with microencapsulated rat islets

Considerations for successful transplantation of encapsulated pancreatic islets

Insulin secretion by rat islet isografts of a defined endocrine volume after transplantation to three different sites

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