Critical mass of purified islets that induce normoglycemia after implantation into dogs

Warnock, Garth L.; Rajotte, Ray V.

doi:10.2337/diabetes.37.4.467

Cited by 55 publications

(37 citation statements)

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“…The results of the present study support our hypothesis and show that islet transplantation to the pancreas may correct both diabetes and pancreatic digestive insufficiency. Normalization of both conditions is likely dependent on the number of islets implanted, as it is known that a minimum islet number is required to prevent diabetes in islet recipients [18,19]. The rat model received the accepted minimum for a renal site transplant in both the kidney and the pancreas, which is approximately one-half to one-third of the pancreatic islet complement.…”

Section: Discussionmentioning

confidence: 99%

“…The dog received a mean of 7600 ± 3600 islets/kg body weight. The minimum number of islets required to prevent diabetes has been suggested to be 5000/kg in the dog [19]. It is reasonable to assume that scattering of the islets throughout the pancreas is more effective than concentrating the transplant into one area, as more acinar tissue is served.…”

Section: Discussionmentioning

confidence: 99%

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Remission of Digestive Insufficiency by Islet Transplantation to the Pancreas

2006

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Pancreatic digestive insufficiency is a common problem in both Type 1 and Type 2 diabetes and remains a serious consequence of diabetes in developing countries. The problem is not corrected by supportive therapies including exogenous insulin injections. It is our hypothesis that digestive insufficiency may be corrected or diminished by the transplantation of islets to the pancreas, thereby supplying islet hormones directly to acinar tissue analogous to the normal pancreas. Diabetic rats received 1000 syngeneic islets and dogs received 7600 autologous islets per kilogram as a transplant to the pancreas. Blood glucose and amylase concentrations were normalized in islet recipients in contrast with controls receiving no islets or islets transplanted to the renal capsule. These results suggest that diabetic digestive insufficiency may be corrected by intrapancreatic islet transplantation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Remission of Digestive Insufficiency by Islet Transplantation to the Pancreas

2006

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“…Purification of the islets was performed by centrifugation on Ficoll discontinuous gradients by a modification of the method of Warnock and Rajotte. 11 First, 4-ml aliquots of digested tissue suspended in M199 (Gibco BRL, Grand Island, NY, USA) were placed in a 50-ml conical tube, then 4.3 ml of 5ϫM199 and 16.7 ml of Ficoll (density 1.125) were added to each, and three 5-ml aliquots of Ficoll/M199 at densities of 1.085, 1.075, and 1.045 were layered successively over the tissue suspensions. The tubes were centrifuged at 800 ϫ g for 20 min.…”

Section: Islet Isolationmentioning

confidence: 97%

Humoral Human Xenoreactivity Against Isolated Pig Pancreatic Islets

et al. 2000

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It is widely believed that the hyperacute rejection of vascularized xenografts in the pig-to-human combination is triggered by the binding of human preformed natural antibodies (PNAbs) to the Galalpha.(1,3)Gal epitope in pig endothelium and the subsequent activation of complement. However, it remains poorly defined whether xenogeneic pig pancreatic islets are damaged by antibody and complement-mediated mechanisms. We examined the expression of Galalpha(1,3)Gal on isolated adult pig islets and the presence of PNAbs in normal human sera directed against islets, using immunofluorescence staining and confocal laser scanning microscopy. The pig islets were not stained with Galalpha(1,3)Gal-specific lectin GSIB4, however, the exocrine cells reacted strongly with GSIB4, indicating that the Galalpha(1,3)Gal epitope was highly expressed on exocrine cells, but not on islets. Human sera showed weak reactivity of IgM and IgG class PNAbs to the islets, but strong reactivity to the exocrine cells. Furthermore, we investigated the cytotoxic effect of human serum on pig islets using an in vitro model of pig-to-human islet transplantation. The incubation of pig islets with normal human sera for 45 min resulted in less than 10% specific lysis despite the binding of PNAbs, whereas exposure of porcine aortic endothelial cells to the same human sera caused 56% complement-mediated lysis, determined using a MTT cytotoxic assay. These results support the view that pig islets might not undergo early antibody and complement-mediated rejection in humans.

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“…So konnten pro Pankreas zwischen 6real 104 und 3mal 106 Inseln und inseltragende pankreatische Fragmente gewonnen werden. Diese Zahlen decken sich mit den Ergebnissen anderer Untersucher [20,23,32], wobei beachtet werden muB, dab in unseren Experimenten sowohl Inseln als auch inseltragende Fragmente gez~ihlt wurden. In jfingster Zeit sind wir dazu fibergegangen, zus/itzlich zur Z/ihlung Neutralrot gef/irbter Inseln und Fragmente eine spezifische F/irbung zur Inselidentifikation mit Dithizone [11,19,32] [21].…”

Section: Diskussionunclassified

In-vitro- und In-vivo-Studien zur Isolierung, Transplantation und Funktion von Langerhans-Inseln am Schwein

Hesse¹,

Danis²,

Weyer³

et al. 1990

Langenbecks Arch Chir

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Limits and possibilities of the transplantation of islets of Langerhans in pigs were studied. 6 x 10(4) to 3 x 10(6) islets and insulin producing fragments per pancreas were obtained by intraductal collagenase digestion of the pancreatic gland following total pancreatectomy. Islets grafted into the spleen or liver rendered normoglycemia to the pancreatectomized animals as demonstrated by normal fasting blood sugars and normal intravenous glucose tolerance tests as compared to not operated animals permitting a survival time of up to one year. Apancreatic controls died of ketoacidosis and diabetic coma 10 to 12 days posttransplant. The number of isolated and transplanted islets correlated well to the normoglycemic state of the animal. Beyond that the in vitro challenge of the islets with glucose and resulting insulin secretion was a very important indicator for the functional status and integrity of the islets after transplantation. Thus the pig appears to be a suitable model for the preclinical studying of islet transplantation especially since immunologic, physiologic and anatomic features of the pig are similar to those in the human regarding pancreas and nutrition.

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Critical mass of purified islets that induce normoglycemia after implantation into dogs

Cited by 55 publications

References 0 publications

Remission of Digestive Insufficiency by Islet Transplantation to the Pancreas

Remission of Digestive Insufficiency by Islet Transplantation to the Pancreas

Humoral Human Xenoreactivity Against Isolated Pig Pancreatic Islets

In-vitro- und In-vivo-Studien zur Isolierung, Transplantation und Funktion von Langerhans-Inseln am Schwein

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