Improved Allograft Survival Using Highly Enriched Populations of Rat Islets

Selawry, Helena; Mui, Mei Mei; Paul, Ronald D.; Distasio, John A.

doi:10.1097/00007890-198402000-00016

Cited by 8 publications

(4 citation statements)

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“…In the hamster, 1 wk culture at 240C and 370C, respectively, does not influence the islet graft's potential for angiogenesis and revascularization ( 18). However, it has been reported that up to 50% of rat islets are lost in tissue culture or after transplantation within five to seven days after isolation ( 19,20), and it was hypothesized that islet and/or B cell ischemia may be responsible for functional failure ofislet transplants. To exclude influences ofislet culture on their potential for revascularization, in the present study islet grafting was performed immediately after the isolation procedure.…”

Section: Resultsmentioning

confidence: 99%

Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts.

Menger¹,

Vajkoczy²,

Leiderer³

et al. 1992

J. Clin. Invest.

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The influence of hyperglycemia on the microvascular blood perfusion of pancreatic islet isografts of Syrian golden hamsters was analyzed by direct visualization ofthe islet's microvasculature by means of in vivo fluorescence microscopy. The experiments were performed using the hamster dorsal skinfold preparation, which allows for quantitative analysis of the microcirculation of islets grafted on the striated skin muscle. Islets were isolated from inbred hamsters by collagenase digestion and subsequently transplanted in normoglycemic (controls; n = 8) and hyperglycemic (65 mg/kg streptozotocin intravenously; n = 10) recipients. In both groups, revascularization of the islet grafts was completed on day 10 after transplantation. Quantitative analysis of capillary blood perfusion on days 6, 10, and 14 revealed no differences in functional capillary density and capillary red blood cell velocity of islets grafted into normoglycemic as compared to hyperglycemic animals. However, islet capillaries were significantly wider in hyperglycemic recipients (11.9±1.3 gm, P < 0.01) as compared to normoglycemic controls (8.9±0.4 Mm). The increase of capillary diameters resulted in a significant rise (P < 0.01) of mean capillary blood perfusion from 1.76±0.39 nl/min in controls to 2.88±0.63 nl/min in hyperglycemic recipients, indicating an increase in microvascular blood perfusion due to hyperglycemia. From these results it is concluded that hyperglycemia is associated with higher capillary blood perfusion in revascularized islet isografts, similarly as known for pancreatic islets in situ. (J. Clin. Invest. 1992. 90:1361-1369.) Key words: intravital fluorescence microscopy*quantitative microcirculatory analysis * hamster * revascularization * islet microvasculature

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Section: Resultsmentioning

confidence: 99%

Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts.

Menger¹,

Vajkoczy²,

Leiderer³

et al. 1992

J. Clin. Invest.

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“…The goal of this study was to compare the survival times of islet allografts in three different organ sites, namely, the liver, under the renal capsule, and intratesticular with the testis either in the scrotum or in the abdominal cavity. For this purpose the Wistar-Lewis rat, which has been shown to be quite resistant to islet transplantation, 7 was selected as the recipient of islet allografts of ACI donor rats and the survival times of the grafts in the three different organ sites were investigated. The results will show that islets remained functional only in those testicles that had been surgically implanted in the abdominal cavity after transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…Islets were isolated according to the method of Lacy and Kostianovsky 8 and purified by means of Ficoll gradient centrifugation as described recently by our laboratory. 7 The islet preparations were then transferred to biologic grade Petri dishes in groups of 300 per dish. Each Petri dish contained 6.0 ml CMRL-1066 medium supplemented with 10% FCS, penicillin (100 U/ml), streptomycin (100 fig/ ml), and glucose at 200 mg/dl.…”

Section: Methodsmentioning

confidence: 99%

Extended Allograft Survival of Islets Grafted into Intra-abdominally Placed Testis

Selawry

Whittington

1984

Diabetes

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Isolated islets of ACI donor rats were cultured for 4 days at 37 degrees C and then grafted into male diabetic Wistar-Lewis rats into three different organ sites without adjuvant immunosuppression. None of 6 recipients of the intraportal injection of 10 islets per gram of body weight became normoglycemic. Similarly, six rats that received islets injected under the renal capsule remained diabetic. None of six rats that received an intratesticular islet allograft became normoglycemic while these organs remained within the scrotum. By contrast, six rats that were transplanted with an identical number of islets into the testis, which were then surgically placed into the abdominal cavity, promptly became aglycosuric and have remained so for more than 50 days.

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“…To obtain total islet protein, islets were isolated by collagenase digestion of total pancreases, using a modified version of a previously described procedure [10]. They were then immersed in an acid-alcohol solution, sonicated and left overnight at 4°C.…”

Section: Islet Insulin Contentmentioning

confidence: 99%

Pancreatic islets from cyclin-dependent kinase 4/R24C (Cdk4) knockin mice have significantly increased beta cell mass and are physiologically functional, indicating that Cdk4 is a potential target for pancreatic beta cell mass regeneration in Type 1 diabetes

Marzo¹,

Mora

Fabregat

et al. 2004

Diabetologia

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Aims/hypothesis. Cyclin-dependent kinase 4 (Cdk4) is crucial for beta cell development. A mutation in the gene encoding for Cdk4, Cdk4R24C, causes this kinase to be insensitive to INK4 cell cycle inhibitors and induces beta cell hyperplasia in Cdk4R24C knockin mice. We aimed to determine whether this Cdk4R24C mutation also affects proper islet function, and whether it promotes proliferation in human islets lentivirally transduced with Cdk4R24C cDNA. Methods. Our study was conducted on wild-type and Cdk4R24C knockin mice. Pancreases were morphometrically analysed. Intraperitoneal glucose tolerance tests and intravenous insulin tolerance tests were performed on wild-type and Cdk4R24C mice. We also did in vitro islet perifusion studies and islet metabolic labelling analysis. Human islets were transduced with Cdk4R24C cDNA. Results. Pancreatic islets from Cdk4R24C knockin mice exhibit a larger insulin-producing beta cell area and a higher insulin content than islets from wild-type littermates. Insulin secretion in response to glucose is faster and reaches a higher peak in Cdk4R24C mice without leading to hypoglycaemia. Conversion of proinsulin into insulin and its intermediates is similar in Cdk4R24C and wild-type mice. Glucose utilisation and oxidation measured per islet were similar in both experimental groups. Insulin secretion was faster and enhanced in Cdk4R24C islets perifused with 16.7 mmol/l glucose, with slower decay kinetics when glucose returned to 2.8 mmol/l. Moreover, human islets expressing Cdk4R24C cDNA exhibited higher beta cell proliferation. Conclusions/interpretation. Despite their hyperplastic growth, Cdk4R24C insulin-producing islet cells behave like differentiated beta cells with regard to insulin production, insulin secretion in response to glucose, and islet glucose metabolism. Therefore Cdk4 could possibly be used to engineer a source of beta cell mass for islet transplantation.

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Improved Allograft Survival Using Highly Enriched Populations of Rat Islets

Cited by 8 publications

References 0 publications

Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts.

Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts.

Extended Allograft Survival of Islets Grafted into Intra-abdominally Placed Testis

Pancreatic islets from cyclin-dependent kinase 4/R24C (Cdk4) knockin mice have significantly increased beta cell mass and are physiologically functional, indicating that Cdk4 is a potential target for pancreatic beta cell mass regeneration in Type 1 diabetes

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