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R G Bretzel

Publications and source records attributed to R G Bretzel.

At least 19 recordsLinked to original sources
PubMed2006

[Sandfly fever Naples virus (serotype Toscana) infection with meningeal involvement after a vacation in Italy].

HISTORY AND CLINICAL FINDINGS: A 69-year-old man was admitted to our hospital with severe headache, recurrent episodes of fever and deterioration of general health. He returned from a vacation in Tuscany (Italy) a few days before admission. Physical examination revealed slight nuchal rigidity and an elevated body temperature of 37.8 C but was otherwise unremarkable. INVESTIGATIONS: Differential blood count showed a lymphocytopenia. Other abnormal laboratory findings included an elevated blood sedimentation rate and a slightly increased C-reactive protein value. Abdominal sonography demonstrated a marginally enlarged spleen. DIAGNOSIS, TREATMENT AND CLINICAL COURSE: A lumbar puncture was performed. Cerebrospinal fluid analysis revealed a lymphocytic meningitis. Serological examination of a blood sample showed specific IgM-antibodies against sandfly fever Naples virus (SFNV), subtype Toscana virus (TOSV). After this diagnosis had been made initially instituted intravenous administration of antibiotics and antiviral medication were discontinued. The patient's symptoms improved rapidly under symptomatic treatment. Slight headaches without episodes of fever persisted for a few weeks without residual neurological symptoms. CONCLUSIONS: A history of travel should always be sought in patients with clinical signs for meningitis. Considering the increasing spread and incidence of SFNV and its subtype Toscana in mediterranean countries, such virus should be kept in mind when treating patients who present such symptoms after returning from those countries during the summer season.

Acyclovir↗
PubMed2006

High prevalence of vitamin D deficiency, secondary hyperparathyroidism and generalized bone pain in Turkish immigrants in Germany: identification of risk factors.

INTRODUCTION: The aim of the study was to determine the prevalence of vitamin D deficiency, secondary hyperparathyroidism (sHPT), generalized bone pain and predictors of vitamin D deficiency in a cohort of 994 healthy adult urban residents (589 males, 405 females; age range: 16-69 years) consisting of 101 Germans, 327 Turkish residents of Turkey and 566 Turkish immigrants living in Germany. METHODS: The mean (+/- standard deviation) for 25-hydroxyvitamin D [25(OH)D] and biointact parathyroid hormone (BioPTH) for the German men and women was 68.4 nmol/l and 26.7 pg/ml, respectively. Turkish residents of Turkey had a mean 25(OH)D and BioPTH of 40.6 nmol/l and 27.5 pg/ml, respectively, whereas Turkish residents of Germany had a 25(OH)D of 38.1 nmol/l and a BioPTH of 35.6 pg/ml. RESULTS: Vitamin D insufficiency was common among Turkish nationals independent of whether they lived in Turkey or Germany; 75% had 25(OH)D levels of <50 nmol/l. Turkish females had a higher prevalence of 25(OH)D deficiency (<25 nmol/l) than Turkish males: 30 and 19% of Turkish females living in Germany and Turkey were severely vitamin D deficient compared to 8% and 6% of Turkish males living in Germany and Turkey, respectively. With respect to BioPTH levels, 31% of Turkish females and 21% of Turkish males had elevated BioPTH levels in contrast to only 15% of females and 4% of males living in Turkey. Unconditional logistic regression analysis identified the most important predictors for low 25(OH)D levels as sex, body mass index, lack of sun exposure and living at a higher latitude. Additionally, wearing a scarf and number of children were found to be an independent risk factor for vitamin D deficiency in Turkish women living in Turkey and Germany. A strong correlation between low 25(OH)D levels and higher rates and longer duration of generalized bone and/or muscle aches and pains (often diagnosed as fibromyalgia) was observed. CONCLUSION: Secondary hyperparathyroidism and vitamin D deficiency was found to be common among Turkish immigrants living in Germany, especially in veiled women. Therefore, the monitoring of vitamin D status--i.e. 25(OH)D and PTH--in Turkish immigrants is warranted and once a deficiency is identified, it should be appropriately treated.

Adolescent↗
PubMed2006

[Therapy of diabetes mellitus. Pancreas transplantation, islet transplantation, stem cell and gene therapy].

The long-term normalization of glucose metabolism - a prerequisite for the prevention of secondary complications in patients with diabetes mellitus - is only possible by transplantation of a whole pancreas or a reasonable number of islets. An absolute indication for pancreas grafting is given in type 1 diabetic patients with end-stage renal disease. The 1-year survival after simultaneous kidney/pancreas transplantation is, according to the international registry, 94-100% for patients, 89-92% for kidneys and 85-87% for the pancreas. The high success rate with long lasting normalization of glucose metabolism leads to a stabilization and/or amelioration of secondary complications, to an increase in quality of life and, most importantly, to a significant reduction in mortality when compared to diabetic kidney recipients. The indications for islet transplantation are similar to those for pancreatic grafting. Islet grafting is only a minor surgical procedure, but islet isolation is difficult. The 1-year survival for the recipients is 98%, for the islets 82% and for insulin-independency 42%. There is a significant decline of islet function to 10% 5 years after transplantation. Stem cell therapy would provide a definitive treatment solution not only for patients with type 1 diabetes. So far, this therapeutic option is still at an early stage of development.

Combined Modality Therapy↗
PubMed2006

Ischaemia is linked to inflammation and induction of angiogenesis in pancreatic islets.

Beta-cell replacement is the only way to restore euglycaemia in patients with type-1 diabetes. Pancreatic tissue, processed for subsequent clinical islet transplantation, is exposed to ischaemia causing injury and death in a large number of islets before and after transplantation. In this review we summarize what is known on the sources of environmental stress for pancreatic islets, such as insufficient oxygen supply during pancreas procurement and in culture prior to intraportal transplantation, nutritional and oxygen deprivation during the isolation process, and the consequences of hyperglycaemia. An increasingly recognized role in the modulation of beta-cell function and these environmental stress factors plays the vascular network of the pancreatic islets. Islet revascularization by angiogenesis is relevant for the survival of the graft subsequent to transplantation. Potential strategies offered by therapeutic induction of revascularization to ameliorate the detrimental impact of these factors on the quality of islet transplants are discussed.

Apoptosis↗
PubMed2005

Adiponectin is functionally active in human islets but does not affect insulin secretory function or beta-cell lipoapoptosis.

CONTEXT: The adipokine adiponectin has insulin-sensitizing, antiatherogenic, and antiinflammatory properties. Mouse and human adiponectin receptor-1 and -2 have been cloned, both of which are expressed in various tissues and mediate effects of globular and full-length adiponectin. Whether adiponectin affects insulin secretion and beta-cell apoptosis and whether plasma adiponectin is associated with beta-cell function in humans is under investigation. DESIGN AND METHODS: In human islets from multiorgan donors, we investigated expression of adiponectin receptor-1 and -2. Furthermore, glucose-stimulated insulin secretion was determined by RIA. In addition, we investigated fatty acid-induced beta-cell apoptosis by terminal dUTP nick end labeling and flow-cytometric cell cycle analysis (sub-G1 formation). In humans in vivo, insulin secretory function was measured during hyperglycemic clamps in 65 normal glucose-tolerant subjects. We determined first and second phase of glucose-stimulated, glucagon-like peptide-1-stimulated, and arginine-stimulated insulin secretion. RESULTS: Adiponectin receptor-1 and -2 are expressed in human islets at the mRNA and protein level. Moreover, full-length adiponectin induces phosphorylation of acetyl coenzyme A carboxylase. However, adiponectin did not affect basal or glucose-stimulated insulin secretion or basal or fatty acid-induced beta-cell apoptosis. In vivo, fasting plasma adiponectin concentrations were not associated with glucose-stimulated first- and second-phase insulin secretion or with glucagon-like peptide-1- or arginine-stimulated insulin secretion (all P > 0.42). CONCLUSIONS: These data support a regulatory role of adiponectin in human islets; however, adiponectin does not seem to affect insulin secretion or basal/fatty acid-induced beta-cell apoptosis in humans.

Adiponectin↗
PubMed2005

Effect of stable glutamine compounds on porcine islet culture.

BACKGROUND: Pig islets are characterized by significant fragility, preventing successful islet culture prior to xenotransplantation. To improve outcome after culture, we compared the effects of glutamine supplementation on survival and viability of isolated pig islets during culture. METHODS: Pig islets were suspended in CMRL 1066 supplemented either with 2.5 mmol/L N-acetyl-L-alanyl-L-glutamine (NALG), a stable compound of L-glutamine, or with 2.5 or 5.0 mmol/L of free L-glutamine (L-Glu). After 24 hours of preincubation, islets were stressed for additional 48 hours with H2O2, DETA, or a cytokine mix. RESULTS: Twenty-four-hour survival of unstressed controls precultured with 2.5 mmol/L NALG was significantly decreased compared with islets pretreated with 2.5 or 5.0 mmol/L L-Glu (P < .01). Fresh islets, viability decreased significantly after NALG preincubation, but was maintained after preincubation in 2.5 or 5.0 mmol/L L-Glu (not significant vs fresh; P < .05 vs NALG). Compared with NALG pretreatment L-Glu did not significantly ameliorate the relative survival (related to cultured controls) of islets during proinflammatory treatment. Nevertheless, the beneficial effect of L-Glu preculture on absolute survival (related to freshly isolated islets) of stressed islets was still present in contrast to NALG pretreatment (P < .01). Viability of stressed islets was significantly protected by L-Glu but not by NALG. CONCLUSIONS: Pig islet culture is significantly improved if L-glutamine is administered in an unbound form compared with the stable compound NALG. Stress resistance of pig islets seems to be increased by free L-glutamine as well.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2005

Adjustment of the ratio between collagenase class II and I improves islet isolation outcome.

BACKGROUND: Previous studies have clarified the distinct roles of collagenase class I (ccI) and class II (ccII) in enzymatic release of islets from pancreatic tissue. The present study sought to enhance the limited knowledge about the optimal ratio between collagenase classes. METHODS: Rat islets were isolated utilizing 0.4 DMC-U of neutral protease and 20 PZ-U of fractionated NB-1 collagenase recombined to obtain a ccII/I ratio of 0.5, 1.0, and 1.5. Quality control included assessment of yield (islet equivalents), trypan-blue exclusion, insulin release during static glucose incubation, and transplant function in diabetic nude mice. Data are expressed as mean values +/- SEM. RESULTS: Digestion time was only minimally influenced by different ccII/I ratios. The highest islet yield (P < .05) was obtained using a ccII/I ratio of 1.0. Purity and glucose stimulation index were only marginally affected by different ccII/I ratios. A significant loss of islet viability after 24-hour culture (P < .05) was observed only in islets isolated by means of a ccII/I ratio of 0.5 and 1.5 but not 1.0. Transplantation into diabetic nude mice revealed sustained islet graft function in all experimental groups. CONCLUSIONS: The present study indicates that the ratio between ccII and ccI is of significant relevance for optimizing islet yield and viability.

Animals↗
PubMed2005

[Pyruvate kinase M2 (tumor M2-PK) as a screening tool for colorectal cancer (CRC). A review of current published data].

INTRODUCTION: Colonoscopy is currently supposed to be the best screening tool for colorectal cancer. However, the acceptance of the population is very poor although it has been included in screening programs in the German health system since 2002. Therefore, evaluation of additional screening tools seems to be of great interest. Recently testing for fecal occult blood (FOBT), genetic alterations or alterations in tumor metabolism (e.g., tumor M2-PK) are under investigation. METHODS: The use of M2-PK measurement in the feces has been reported in 6 studies until today. The data of these studies were analyzed and critically reviewed. RESULTS: The overall sensitivity of M2-PK is 77.9% concerning CRC. Specificity ranges from 74.3-83.3%. Overall sensitivity for adenomas is 45.9%, increasing to 61.1% for adenomas > 1 cm. A high percentage of positive results (90.4%) was also observed in patients with chronic inflammatory bowel disease. CONCLUSIONS: Compared to FOBT or genetic testing the M2-PK test seems to be superior for CRC screening. Concerning handling, effectiveness and analysis, M2-PK seems to be a good possibility for large scale-screening of colorectal carcinoma. It might even be used to detect larger adenomas. Elevated levels of M2-PK in patients with acute and/or chronic inflammatory bowel diseases are probably due to proliferation of epithelial cells and leucocytes in the inflammatory area.

Biomarkers, Tumor↗
PubMed2004

Faecal tumour M2 pyruvate kinase: a new, sensitive screening tool for colorectal cancer.

Proliferating cells, especially tumour cells, express a special isoenzyme of pyruvate kinase, termed M2-PK, which can occur in a tetrameric form with a high affinity to its substrate, phosphoenolpyruvate (PEP), and in a dimeric form with a low PEP affinity. In tumour cells, the dimeric form is usually predominant and is therefore termed Tumour M2-PK. The levels of Tumour M2-PK within tumours and in EDTA-plasma correlate with staging and the ability of the tumour cells to metastasise. Since most colorectal tumours grow intraluminally, it appeared interesting to determine whether Tumour M2-PK is detectable in the faeces of tumour patients. Stool samples were tested by ELISA from controls without colorectal cancer and colorectal cancer patients. Whereas Tumour M2-PK levels were low in the control group (mean value+/-s.e.m.: 3.3+/-0.4, n=144), they were high in the case of colorectal cancer (56.1+/-15.3, n=60). At a cutoff value of 4 U ml(-1), the sensitivity was 73%. TNM and Dukes' classification of the tumours revealed a strong correlation between faecal Tumour M2-PK levels and staging. The determination of Tumour M2-PK in faeces provides a new promising screening tool for colorectal tumours.

Biomarkers, Tumor↗
PubMed2004

Disseminated periportal fatty degeneration after allogeneic intraportal islet transplantation in a patient with type 1 diabetes mellitus: a case report.

Insulin independence after islet transplantation has been significantly improved by using new steroid-free immunosuppressive protocols and increased islet mass. Only little is known about the influence on the morphology of the liver of intraportally transplanted islets. We describe a case of disseminated periportal fatty degeneration after allogeneic intraportal islet transplantation (ITx). A 35-year-old patient with type-1 diabetes mellitus who was suffering from repeated severe hypoglycemic episodes received two sequential intraportal islet grafts. Liver structure was normal before the first ITx, based upon ultrasound and magnetic resonance imaging (MRI). One week after the first ITx, ultrasound demonstrated normal liver morphology. Four months later, at the second ITx, we detected small, disseminated, and hypodense hepatic lesions (1 to 3 mm) by ultrasound, which were confirmed by MRI and interpreted to be fatty degenerations. Histologically we found focal drop-shaped fatty degenerations with signs of mild periportal chronic inflammation. These liver alterations without clinical symptoms or pathological liver function tests matched the predicted distribution of infused islets. Glucose metabolism markedly improved after the first ITx, namely 58.6% reduction of daily insulin requirements, 1.4% decrease in HbA1c, basal C-peptide of 0.8 to 1.3 ng/dl with no severe hypoglycemia. We interpreted these benign changes in liver morphology as reactions to a local hyperinsulinemia in the neighborhood of the transplanted islets. We hypothesized that a steroid-free immunosuppression with rapamycin and tacrolimus may have contributed to changes in the portal microenvironment.

Adult↗
PubMed2004

The role of current product release criteria for identification of human islet preparations suitable for clinical transplantation.

BACKGROUND: Alloimmunity, autoimmunity, and nonspecific inflammation are known to be potential determinants for long-term islet survival and insulin independence. Sufficient islet mass is a key determinant. But islet engraftment and posttransplant survival may also depend on functional characteristics of the graft. This study investigated the significance of current product release criteria for the transplantation outcome. METHODS: Fourty five consecutive transplanted human islet preparations and their functional outcomes were analyzed. Islet mass was determined according to standard criteria: purity by light microscopy, viability by dye exclusion and Insulin secretory response to static glucose incubation. Islet graft function was monitored for > or = 1 year. Islet function was defined as full (FF), partial (PF), or nonfunction (NF) based on serum C-peptide levels and insulin independence. RESULTS: All islet grafts displayed primary function. Islet mass [IEQ/kg BW]: 7331.3 +/- 679.7 (FF), 5821.3 +/- 546.7 (PF), 6468.6 +/- 658.5 (NF), (FF vs PF p = .032) Purity [%] 86.9 +/- 3.1 (FF), 76.0 +/- 2.87 (PF), 88.2 +/- 2.3 (NF) (FF vs PF P =.045, PF vs NF, P = 0.01). (4) Viability [%]:89.2 +/- 2 (FF), 86.2 +/- 1.7 (PF), 87.3 +/- 1.8 (NF) (ns). Stimulation index (SI): 20 +/- 6.3 (FF), 80.2 +/- 28.2 (PF), 21.6 +/- 3.5 (NF) (ns) No correlation was observed between SI and any other parameter nor between SI and C-peptide levels. Islet mass significantly correlated with C-peptide levels at 6 and 12 months after transplantation for functioning grafts. CONCLUSIONS: Stringent product release criteria allow identification of islet preparations suitable for clinical transplantation. However, currently used parameters are not predictive of long-term graft function, indicating that further refined quality assessments including apoptosis and resistance to early inflammation, are required to assess the primary engrafted islet mass.

Automation↗
PubMed2004

Can the density of native pancreatic tissue slices predict human islet isolation and purification outcome?

INTRODUCTION: With currently available technology, the outcomes of human islet isolation and purification are still inconsistent, in part due to a lack of control of the pancreas donor and the procurement conditions. Using a single donor pancreas, the critical islet mass for establishing insulin independence of approximately 5000 engrafted islet equivalents (IEQ)/kg of recipient weight can only be retrieved from about one third of isolations. The purpose of this study was to analyze whether successful islet isolation and purification outcomes might be predicted from the density of native pancreatic tissue. METHODS: Tissue slices (TS) were obtained from the neck of 9 nondistended human donor pancreata. The density of the TS was determined using gravity sedimentation in continuous density gradients under either iso-osmolar or hyperosmolar conditions. Correlation coefficients were calculated with regard to the density of isolated exocrine and endocrine tissue, donor age, body mass index (BMI), cold ischemia time (CIT), IEQ prepurification and postpurification, IEQ recovery, and purity. RESULTS: (1) There was no change in density over time for TS in 300 mOsm/kg (mean, 1.079 +/- 0.0019 g/cm(3)) (2) In 500 mOsm/kg, there was a significant increase in density from 1.086 +/- 0.0021 g/cm(3) to 1.092 +/- 0.0021 g/cm(3) over time. (3) Density of isolated exocrine and endocrine became more distinct with lower density of TS (r = -0.776; P < .05). (4) Donor age, BMI, recovery of IEQ from gradients, and number of IEQ after purification did not correlate significantly with TS density. (5) In contrast, a significant inverse correlation existed betwen TS and CIT (r = -0.829; P < .05), and between TS versus IEQ number prior to purification (r = -0.867; P < .05). CONCLUSION: No homogeneous distribution of pancreas tissue density was seen among 9 consecutive human organs. Taken together, the density of native pancreas TS is not a suitable sole predictor for successful islet isolation and purification.

Adult↗
PubMed2004

Optimization in osmolality and range of density of a continuous ficoll-sodium-diatrizoate gradient for isopycnic purification of isolated human islets.

INTRODUCTION: According to previous estimates from large animals and man, a minimum of approximately 5000 to 6000 engrafted islet equivalents (IEQ)/kg recipient weight is critical to establish insulin independence. Utilizing a single donor, this threshold yield of purified islets can be retrieved from approximately one third of all isolations. The aim of this study was to improve human islet purification by optimization of the osmolality and the density range of the continuous Ficoll-sodium-diatrizoate (FSD) gradient to facilitate consistent purities >80% of human islet preparations without considerable loss of islet yield. METHODS: Aliquots of human pancreatic digests were placed on continuous density gradients. After centrifugation, sequential aliquots were extracted for amylase and insulin to determine the relative and cumulative density distribution of endocrine and exocrine tissue. We addressed the impact of two factors: (1) osmolalities (300 to 600 mosm/kg) in the gradient of FSD covering a density range of 1.070 to 1.100 g/cm(3); and (2) density (FSD 500/1.070 to 1.100) versus density-osmolarity gradient (DO-FSD 400-530/1.080 to 1.113). RESULTS: The density of exocrine and endocrine tissue increased with rising osmolality. Differences in density of both tissues were highest at 450 and lowest at 300 and 600 mOsmol/kg. Purity and recovery were highest at 450 versus 400 or 500 mOsm/kg (NS). Exocrine but not endocrine tissue was more dense in DO-FSD than in FSD gradient (P < .05). The differences in density were 0.004 versus 0.013 g/cm(3) (P < .01), resulting in an increased islet purity and recovery. CONCLUSION: The best osmolality for the FSD 1.070 to 1.100 g/cm(3) is at 450 mOsm/kg. Using the DO-FSD may improve human islet purification allowing successful clinical islet transplantation.

Cell Count↗
PubMed2004

Intensive insulin regimens: evidence for benefit.

It is now well established that the risk of experiencing diabetic complications is dependent on the degree of glycaemic control in patients with diabetes. Clinical trials such as the Diabetes Control and Complications Trial (DCCT) and Kumamoto study have demonstrated that tight glycaemic control achieved with intensive insulin regimens can reduce the risk of developing or progressing retinopathy, nephropathy or neuropathy in patients with type I or II diabetes. The EDIC trial, a follow-up to the DCCT, has shown that the previous degree and duration of glycaemic exposure are also important determinants of risk of developing microvascular diabetic complications. It appears that beneficial outcomes with regard to microvascular risk can be achieved with the improved metabolic control associated with intensive insulin regimens; however, data examining the effect of intensive insulin regimens on macrovascular risk is inconclusive. Epidemiological data highlight the role of postprandial blood glucose in cardiovascular disease and mortality, especially in patients with type II diabetes. Consequently, it is logical to suppose that insulin regimens that control both fasting plasma glucose and postprandial glucose excursions should also achieve the best macrovascular risk outcomes and there are some data that suggest this. Intensive insulin treatment can also improve prognosis in acute clinical situations such as myocardial infarction in patients with or without diabetes. In summary, intensive insulin regimens achieve strict metabolic control in patients with diabetes and could offer the best possible outcomes with regard to microvascular and macrovascular complications.

Blood Glucose↗
PubMed2004

Diagnostic algorithm and management of immune-mediated complications associated with subcutaneous insulin therapy.

Immune mediated complications associated with subcutaneous insulin therapy such as insulin neutralizing antibodies and/or skin reactions are rare conditions since human insulin is in general use. Nevertheless, if it occurs, a stepwise diagnostic approach is essential for differential diagnosis and consecutive treatment of these complications. Here we suggest a diagnostic algorithm to deal with e.g. insulin antibody formation of the IgG and/or IgE type and/or severe skin reactions resulting in poor metabolic control and often "brittle diabetes" in affected patients. This diagnostic algorithm includes step 1: Intradermal skin testing with positive and negative controls, additives and different insulin preparations; step 2: Quantification of insulin specific IgG and IgE in the serum, and step 3: Analysis of the time dependent binding/dissociation curves of the insulin neutralizing antibodies in an ex vivo/in vitro assay to assess the clinical significance of these antibodies. Based on 158 insulin treated control subjects and four patients with typical symptoms and signs representing the spectrum of immune-mediated complications subsequent to subcutaneous insulin therapy we demonstrate that the proposed stepwise approach leads to a definite diagnosis as a prerequisite for individual and successful therapy.

Adult↗
PubMed2004

Pancreatic islet and stem cell transplantation: new strategies in cell therapy of diabetes mellitus.

Long-term studies strongly suggest that tight control of blood glucose can prevent the development and retard the progression of chronic complications of type 1 diabetes mellitus. In contrast to conventional insulin treatment, replacement of a patient's islets of Langerhans either by pancreas organ transplantation of by isolated islet transplantation is the only treatment to achieve a constant normoglycemic state and avoiding hypoglycemic episodes, a typical adverse event of multiple daily insulin injections. However, the expense of this benefit is still the need for immunosuppressive treatment of the recipient with all its potential risks. Islet cell transplantation offers the advantage of being performed as a minimally invasive procedure, in which islets can be perfused percutaneously into the liver via the portal vein. As of June 2003, 705 pancreatic islet transplants worldwide have been reported to the International Islet Transplant Registry (ITR) at our Third Medical Department, University of Giessen/Germany. Data analysis shows at 1 year after adult islet transplantation a patient survival rate of 97%, a functioning islet graft in 54% of the cases, whereas insulin independence was meanwhile achieved in 20% of the cases. However, using a novel protocol established by the Edmonton Center/Canada, the insulin independence rates have improved significantly reaching meanwhile a 50-80% level. Finally, the concept of islet cell or stem cell transplantation is most attractive since it offers many perspectives: islet cell availability could become unlimited and islet or stem cells my be transplanted without life-long immunosuppressive treatment of the recipient, just to mention 2 of them.

Animals↗
PubMed2003

Angiogenic capacity of endothelial cells in islets of Langerhans.

Transplantation of pancreatic islets reconstitutes glucose homeostasis in diabetes mellitus. Before transplantation, islets are disrupted from the surrounding blood vessels by the isolation procedure, with the grafted tissue being subject to ischemic damage. The survival of transplanted islets is assumed to depend on effective revascularization. Perfusion studies suggest that newly formed microvessels supplying the graft with nutrients are exclusively rebuilt by the host. It is generally not known whether isolated islets contain endothelial cells (EC), which potentially participate in the revascularization process. Therefore, we tried to detect immature EC in isolated islets by transformation with polyoma middle T antigen. Endothelioma cells were generated, implicating the presence of de-differentiated EC within isolated islets. When embedded in a fibrin gel, the islets developed cellular cords consisting of EC, whereas FGF-2 and VEGF stimulated the formation of cord-like structures. Furthermore, we studied the presence of donor EC in islet grafts by using transgenic mice with an EC lineage-specific promotor-LacZ reporter construct (Tie-2LacZ). Following islet transplantation, Tie-2LacZ-positive EC of both donor and recipient were identified in the vicinity of or within the graft up to 3 wk after transplantation. In conclusion, EC and/or their progenitors with angiogenic capacity reside within isolated islets of different species, and their proliferative potential can be stimulated by various inducers. These graft-related endothelia persist after islet transplantation and are integrated within newly formed microvessels.

Animals↗