BACKGROUND: Islet transplantation represents an established therapeutic option for people with type 1 diabetes who have hypoglycemia unawareness syndrome and frequent problematic hypoglycemic episodes when other methods comprising diabetes education and use of technological support fail. Because the current standard method of islet infusion into the liver has some limitations, novel approaches are under investigation. METHODS: We report our first results with 2 cases of islet transplantation into an omental pouch using a biocompatible plasma-fibrin gel. The recipients received 12,350 and 5,350 islet equivalents per kilogram that were mixed with autologous plasma, seeded during a laparoscopic procedure on the omentum, overlaid with human thrombin solution, and fixed by flapping the omentum over. RESULTS: During a 9-month follow-up, neither patient experienced any moderate or severe hypoglycemia. Their glucose control significantly improved, insulin dose decreased by approximately 50%, and C-peptide at 1 year was 0.22 and 0.14 pmol/mL, respectively. The postoperative course was uneventful, but C-peptide production in the first patient progressively declined at 1 year and hypoglycemic episodes recurred. CONCLUSIONS: Though the results for these first 2 cases are not fully satisfactory, we have demonstrated the feasibility, safety, and ability of this novel method to restore insulin production. Further refinements to improve immediate islet survival seem necessary.

• MeSH
• biomedicínský výzkum * MeSH
• C-peptid MeSH
• diabetes mellitus 1. typu * farmakoterapie   chirurgie   MeSH
• hypoglykemie * farmakoterapie   MeSH
• hypoglykemika terapeutické užití   MeSH
• inzulin terapeutické užití   MeSH
• krevní glukóza MeSH
• Langerhansovy ostrůvky * MeSH
• lidé MeSH
• omentum chirurgie   MeSH
• thrombin terapeutické užití   MeSH
• transplantace Langerhansových ostrůvků * škodlivé účinky   metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Instant Blood-Mediated Inflammatory Reaction (IBMIR) is a major cause of graft loss during pancreatic islet transplantation, leading to a low efficiency of this treatment method and significantly limiting its broader clinical use. Within the procedure, transplanted islets obstruct intrahepatic portal vein branches and consequently restrict blood supply of downstream lying liver tissue, resulting typically in ischemic necrosis. The extent of ischemic lesions is influenced by mechanical obstruction and inflammation, as well as subsequent recanalization and regeneration capacity of recipient liver tissue. Monitoring of immediate liver perfusion impairment, which is directly related to the intensity of post-transplant inflammation and thrombosis (IBMIR), is essential for improving therapeutic and preventive strategies to improve overall islet graft survival. In this study, we present a new experimental model enabling direct quantification of liver perfusion impairment after pancreatic islet transplantation using ligation of hepatic arteries followed by contrast-enhanced magnetic resonance imaging (MRI). The ligation of hepatic arteries prevents the contrast agent from circumventing the portal vein obstruction and enables to discriminate between well-perfused and non-perfused liver tissue. Here we demonstrate that the extent of liver ischemia reliably reflects the number of transplanted islets. This model represents a useful tool for in vivo monitoring of biological effect of IBMIR-alleviating interventions as well as other experiments related to liver ischemia. This technical paper introduces a novel technique and its first application in experimental animals.

• MeSH
• embolie * komplikace   diagnóza   MeSH
• ischemie * diagnostické zobrazování   etiologie   MeSH
• játra * krevní zásobení   diagnostické zobrazování   patologie   MeSH
• krysa rodu rattus MeSH
• magnetická rezonanční angiografie metody   MeSH
• přežívání štěpu MeSH
• reprodukovatelnost výsledků MeSH
• teoretické modely MeSH
• transplantace Langerhansových ostrůvků škodlivé účinky   MeSH
• vena portae * MeSH
• vylepšení obrazu metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Pancreas transplantation (PTx) represents the method of choice in type 1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. In 2005, the Institute for Clinical and Experimental Medicine (IKEM) launched a program to investigate the safety potential of islet transplantation (ITx) in comparison to PTx. AIM: This study aims to compare the results of PTx and ITx regarding severe hypoglycemia elimination, metabolic control, and complication rate. METHODS: We analyzed the results of 30 patients undergoing ITx and 49 patients treated with PTx. All patients were C-peptide-negative and suffered from hypoglycemia unawareness syndrome. Patients in the ITx group received a mean number of 12,349 (6,387-15,331) IEQ/kg/person administered percutaneously into the portal vein under local anesthesia and radiological control. The islet number was reached by 1-3 applications, as needed. In both groups, we evaluated glycated hemoglobin, insulin dose, fasting and stimulated C-peptide, frequency of severe hypoglycemia, and complications. We used the Mann Whitney test, Wilcoxon signed-rank test, and paired t-test for analysis. We also individually assessed the ITx outcomes for each patient according to recently suggested criteria established at the EPITA meeting in Igls. RESULTS: Most of the recipients showed a significant improvement in metabolic control one and two years after ITx, with a significant decrease in HbA1c, significant elevation of fasting and stimulated C-peptide, and a markedly significant reduction in insulin dose and the frequency of severe hypoglycemia. Seventeen percent of ITx recipients were temporarily insulin-independent. The results in the PTx group were comparable to those in the ITx group, with 73% graft survival and insulin independence in year 1, 68% 2 years and 55% 5 years after transplantation. There was a higher rate of complications related to the procedure in the PTx group. Severe hypoglycemia was eliminated in the majority of both ITx and PTx recipients. CONCLUSION: This report proves the successful initiation of pancreatic islet transplantation in a center with a well-established PTx program. ITx has been shown to be the method of choice for hypoglycemia unawareness syndrome, and may be considered for application in clinical practice if conservative options are exhausted.

• MeSH
• C-peptid krev   MeSH
• diabetes mellitus 1. typu epidemiologie   etiologie   terapie   MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• hypoglykemie epidemiologie   terapie   MeSH
• krevní glukóza metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• následné studie MeSH
• přežívání štěpu MeSH
• retrospektivní studie MeSH
• syndrom MeSH
• transplantace Langerhansových ostrůvků * škodlivé účinky   metody   MeSH
• transplantace slinivky břišní * škodlivé účinky   metody   MeSH
• výběrové chování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Permanent hyperinsulinemia and the resulting overstimulation of the insulin receptor signaling pathway is suspected as a trigger of cancer genesis in the livers of type 2 diabetic patients. Liver tissue (LT) surrounding transplanted pancreatic islets (PI) can be permanently exposed to insulin in even higher concentrations than in type 2 diabetic patients. Therefore, this study examines the effect of PI transplantation (Tx) on LT in animals with streptozotocin (STZ)-induced diabetes mellitus. The suboptimal mass (400 or 1000) of isogeneic PI was transplanted into either the portal vein or under the kidney capsule of diabetic Brown Norway (BN) rats. Healthy BN rats treated with 400 isogeneic PI transplanted in the portal vein served as a control group. During the first 6 months after PI Tx, small and infrequent cystic lesions developed in animals with STZ diabetes, irrespective of the Tx site. In 10 months, frequent and complex cystic lesions appeared in these animals. In the control group, several small lesions were detected but not until 10 months after the PI Tx. In summary, STZ is the likely main inductor of hepatic cystic lesions, but the contribution of PI was not confirmed.

• MeSH
• cysty etiologie   MeSH
• experimentální diabetes mellitus komplikace   MeSH
• heterotopická transplantace * MeSH
• inzulin metabolismus   MeSH
• játra * MeSH
• krysa rodu rattus MeSH
• Langerhansovy ostrůvky patologie   MeSH
• nádory jater etiologie   MeSH
• potkani inbrední BN MeSH
• streptozocin MeSH
• transplantace Langerhansových ostrůvků škodlivé účinky   MeSH
• vena portae chirurgie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This study evaluated the ability of magnetic resonance imaging (MRI) to predict failure of pancreatic islets (PI) transplanted into the hepatic portal vein. Brown-Norway (n = 18) and Lewis (n = 6) rats received islets isolated from Lewis donors. The rejection process in Brown-Norway recipients was mitigated by two different immunosuppressive regimens [tacrolimus + hydrocortisone for 3 months (n = 6) or tacrolimus for 12 days (n = 12)]. Longitudinal MRI monitoring of recipients at post-transplantation weeks 1, 2, 3, 4, 6, 8, 10, and 12 confirmed the ability to detect SPIO labeled PI after transplantation into the liver. The relative number of MRI signals related to PI isografts remained stable up to study completion. Recipients of PI allografts were normoglycemic until the end of study; signals declined gradually to 44 ± 17% in these animals. In animals with islets failure during post-transplant week 12, the number of signals decreased to 25 ± 10% of initial values. The difference between groups (islet function/failed) became significant post-transplant week 3. Our data demonstrate that the MRI changes attributable to rejection become apparent within 3 weeks after transplantation, i.e. at least 8 weeks before functional allograft failure.

• MeSH
• homologní transplantace MeSH
• krysa rodu rattus MeSH
• Langerhansovy ostrůvky fyziologie   MeSH
• magnetická rezonanční tomografie metody   MeSH
• potkani inbrední BN MeSH
• potkani inbrední LEW MeSH
• rejekce štěpu MeSH
• transplantace Langerhansových ostrůvků škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Simultánní transplantace ledviny a Langerhansových ostrůvků (LO) je v současné době léčebnou alternativou pro pacienty s diabetem 1. typu a chronickým selháním ledvin, kteří nejsou pro vyšší operační riziko vhodní k orgánové transplantaci ledviny a pankreatu. Transplantace LO představuje ve srovnání s transplantací celého pankreatu menší riziko pooperačních komplikací, na druhou stranu je dlouhodobě stále ještě méně efektivní.

Simultaneous kidney and islet transplantation is recent therapeutic alternative for diabetics with end-stage kidney disease, who are not acceptable for simultaneous pancreas-kidney transplantation. Islet transplantation has less complications but still worse long-term function compared to whole pancreas transplantation.

• Klíčová slova
• diabetes,
• MeSH
• chronické selhání ledvin chirurgie   MeSH
• diabetes mellitus 1. typu chirurgie   MeSH
• diabetické nefropatie chirurgie   MeSH
• lidé MeSH
• pankreas MeSH
• transplantace Langerhansových ostrůvků škodlivé účinky   MeSH
• transplantace ledvin MeSH
• transplantace slinivky břišní MeSH
• Check Tag
• lidé MeSH

Organ pancreas transplantation represents the only method enabling long-term normalization of glucose metabolism in type-1 diabetic subjects so far. Unfortunately, surgical complications of this kind of therapy are still frequent. As a safer alternative, transplantation of isolated pancreatic islets was introduced at the Institute for Clinical and Experimental Medicine as a clinical experiment in the year 2005. METHODS AND RESULTS: We isolated the islets from pancreases of cadaveric donors which did not fulfil criteria to perform organ pancreas transplantation. Altogether, 36 islet implantations were performed in 28 C-peptide negative subjects suffering from type-1 diabetes by August 2010. In 15 subjects (21 implantations) the main indication was extremely instable course of diabetes due to the hypoglycaemia unawareness syndrome. In 5 and 3 cases, combined islet and kidney and islet and liver transplants were performed, respectively. In addition, islet autotransplantation was performed in 5 subjects undergoing total pancreatectomy. No patient died during the study period. In all but 1 patient with primary islet afunction, islet transplantation led to a complete cure of the hypoglycemia unawareness syndrome. Out of 15 patients, 11 subjects in this group showed a significant C-peptide production (> 0.2 pmol/ml) after 1 year. The mean insulin dose after allotransplantation decreased from 37 to 14 units per day and in 3 subjects, insulin therapy could be withdrawn. Serious technical complications occurred in 6 subjects, which only in 2 cases required surgical revision and did not cause long-term sequels. CONCLUSIONS: In comparison with organ pancreas transplantation, pancreatic islet transplantation represents a substantially safer method for restitution of endogenous insulin production. Though it eliminates serious hypoglycemic episodes in labile diabetes, complete insulin withdrawal is still often not possible. However, due to continuing progress in the laboratory techniques as well as in the transplant procedure itself, the results are steadily improving.

• Klíčová slova
• slinivka břišní, imunosuprese,
• MeSH
• diabetes mellitus 1. typu farmakoterapie   chirurgie   krev   MeSH
• dospělí MeSH
• hypoglykemika terapeutické užití   MeSH
• inzulin terapeutické užití   MeSH
• komplikace diabetu MeSH
• krevní glukóza analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• transplantace Langerhansových ostrůvků metody   přístrojové vybavení   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• diabetes mellitus 1. typu chirurgie   MeSH
• imunosupresiva škodlivé účinky   MeSH
• lidé MeSH
• pooperační komplikace MeSH
• příprava pacienta k transplantaci MeSH
• rejekce štěpu MeSH
• transplantace Langerhansových ostrůvků metody   škodlivé účinky   MeSH
• transplantace ledvin MeSH
• transplantace slinivky břišní kontraindikace   metody   škodlivé účinky   MeSH
• výběr pacientů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH

• MeSH
• lidé MeSH
• transplantace Langerhansových ostrůvků metody   škodlivé účinky   využití   MeSH
• Check Tag
• lidé MeSH