One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that are simple to use is critical for potential future dissemination of any spinally targeted cell-replacement therapy into general medical practice. Here, we compared the engraftment properties of established human-induced pluripotent stem cells (hiPSCs)-derived neural precursor cell (NPCs) line once cells were harvested fresh from the cell culture or previously frozen and then grafted into striata or spinal cord of the immunodeficient rat. A newly developed human spinal injection device equipped with a spinal cord pulsation-cancelation magnetic needle was also tested for its safety in an adult immunosuppressed pig. Previously frozen NPCs showed similar post-grafting survival and differentiation profile as was seen for freshly harvested cells. Testing of human injection device showed acceptable safety with no detectable surgical procedure or spinal NPCs injection-related side effects.

• MeSH
• buněčná diferenciace fyziologie   MeSH
• dospělí MeSH
• genetické vektory genetika   MeSH
• indukované pluripotentní kmenové buňky * fyziologie   transplantace   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• mícha MeSH
• mozek MeSH
• nervové kmenové buňky * fyziologie   transplantace   MeSH
• odběr biologického vzorku metody   MeSH
• odběr tkání a orgánů metody   MeSH
• prasata MeSH
• přeprogramování buněk * genetika   fyziologie   MeSH
• přežívání štěpu fyziologie   MeSH
• spinální injekce * škodlivé účinky   přístrojové vybavení   metody   MeSH
• transplantace kmenových buněk * škodlivé účinky   přístrojové vybavení   metody   MeSH
• virus Sendai MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Early vascular complications are an acute condition after renal transplantation. They often lead to graft failure, if not intervened immediately. Nowadays, we lack diagnostic means, to monitor graft perfusion continuously. In the project, we would like to develop and test a kidney graft monitoring system that would allow to continuously measure blood perfusion in the early postoperative period. The proposed monitoring system operates on the principle of visible and near infrared light spectroscopy, and allows easy application and removal of the measurement probe. We propose to develop and test a functional prototype and associated surgical procedures, all of which will be tested on animal models (laboratory pigs). The use of the proposed monitoring system promises prevention of a kidney graft failure, resulting in the improvement of patient’s quality of life, shortening the waiting period on the waiting list and considerable economical savings.

Vaskulární komplikace jsou akutním stavem časného pooperačního období po transplantaci ledviny. Pokud nejsou bezodkladně odstraněny, často vedou k selhání štěpu. V dnešní době nemáme diagnostické metody, které by kontinuálně monitorovaly prokrvení štěpu ledviny. V tomto projektu bychom chtěli vyvinout a otestovat systém kontinuální monitorace prokrvení štěpu ledviny v časném pooperačním období. Navrhovaný systém je založen na principu spektroskopie ve viditelné a infračervené oblasti a nabízí jednoduchou aplikaci a odstranění měřícího senzoru. Cílem projektu je vyvinout a vyzkoušet funkční prototyp a zdokonalit příslušnou chirurgickou manipulaci. Experiment bude probíhat na zvířecím experimentálním modelu (laboratorní prase). Využití navrhovaného monitorovacího systému snižuje nebezpečí selhání štěpu ledviny, což vede ke zlepšení kvality pacientova života, snížení čekací doby na čekací listině a významným ekonomickým úsporám.

• MeSH
• blízká infračervená spektroskopie MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• monitorování fyziologických funkcí MeSH
• perfuze MeSH
• pooperační období MeSH
• prasata MeSH
• přežívání štěpu fyziologie   MeSH
• regionální krevní průtok MeSH
• transplantace ledvin MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• hodnotící studie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• nefrologie
• transplantologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

The recurrence of IgA nephropathy (IgAN) after kidney transplantation occurs in 20-35% of patients. The main aim of this study is to evaluate risk factors affecting the course of IgAN after renal biopsy of native kidney and kidney transplant. We evaluated clinical parameters and histological findings at the time of biopsy of native kidney and after kidney transplantation in 313 patients with IgAN with a follow-up of up to 36 years. Using hierarchical clustering method, patients with graft failure (n=50) were divided into two groups based on the mean time from kidney transplant to graft failure (11.2 versus 6.1 years). The time-to-graft failure corresponded well to the time from the renal biopsy of native kidney to end-stage renal disease (5.9 versus 0.4 years). Body mass index, proteinuria, microscopic hematuria, histological evaluation of fibrosis, and crescents at the time of renal biopsy of native kidney were the main variables for the differentiation of the two groups. Higher age of kidney-transplant donor, histological recurrence of IgAN, antibody-mediated rejection, and the onset of microscopic hematuria and proteinuria within 1 year after kidney transplant were also associated with worse graft survival in multivariate Cox regression analysis.

• MeSH
• biopsie MeSH
• chronické selhání ledvin chirurgie   MeSH
• dospělí MeSH
• IgA nefropatie diagnóza   etiologie   patologie   MeSH
• ledviny patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• multivariační analýza MeSH
• přežívání štěpu fyziologie   MeSH
• proporcionální rizikové modely MeSH
• proteinurie patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace ledvin škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

PURPOSE: The liver is the most widely used site for pancreatic islet transplantation. However, several site-specific limitations impair functional success, with instant blood-mediated inflammatory reaction being the most important. The aim of this study was to develop a preclinical model for placement of the islet graft into a highly vascularized omental flap using a fibrin gel. For this purpose, we tested islet viability by bioluminescence imaging (BLI). PROCEDURES: Pancreatic islets were isolated from luciferase-positive and luciferase-negative rats, mixed at a 1:1 ratio, placed into a plasma-thrombin bioscaffold, and transplanted in standard (10 pancreatic islets/g wt; n = 10) and marginal (4 pancreatic islets/g wt; n = 7) numbers into the omentums of syngeneic diabetic animals. For the control, 4 pancreatic islets/g were transplanted into the liver using the standard procedure (n = 7). Graft viability was tested by bioluminescence at days 14, 30, 60, and 90 post transplant. Glucose levels, intravenous glucose tolerance, and serum C-peptide were assessed regularly. RESULTS: Nonfasting glucose levels < 10 mmol/l were restored in all animals. While islet viability in the omentum was clearly detected by stable luminescence signals throughout the whole study period, no signals were detected from islets transplanted into the liver. The bioluminescence signals were highly correlated with stimulated C-peptide levels detected at 80 days post transplant. Glucose tolerance did not differ among the 3 groups. CONCLUSIONS: We successfully tested a preclinical model of islet transplantation into the greater omentum using a biocompatible scaffold made from autologous plasma and human thrombin. Both standard and marginal pancreatic islet numbers in a gel-form bioscaffold placed in the omentum restored glucose homeostasis in recipients with diabetes. Bioluminescence was shown promising as a direct proof of islet viability.

• MeSH
• krysa rodu rattus MeSH
• Langerhansovy ostrůvky diagnostické zobrazování   MeSH
• luminiscenční měření metody   MeSH
• molekulární zobrazování metody   MeSH
• omentum diagnostické zobrazování   MeSH
• přežívání štěpu fyziologie   MeSH
• transplantace Langerhansových ostrůvků * MeSH
• viabilita buněk fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Kidney allograft pathology assessment has been traditionally based on clinical and histological criteria. Despite improvements in Banff histological classification, the diagnostics in particular cases is problematic reflecting a complex pathogenesis of graft injuries. With the advent of molecular techniques, polymerase-chain reaction, oligo- and microarray technologies allowed to study molecular phenotypes of graft injuries, especially acute and chronic rejections. Moreover, development of the molecular microscope diagnostic system (MMDx) to assess kidney graft biopsies, represents the first clinical application of a microarray-based method in transplantation. Whether MMDx may replace conventional pathology is the subject of ongoing research, however this platform is particularly useful in complex histological findings and may help clinicians to guide the therapy.

• MeSH
• alografty metabolismus   MeSH
• diagnostické techniky molekulární metody   trendy   MeSH
• lidé MeSH
• přežívání štěpu fyziologie   MeSH
• rejekce štěpu diagnóza   genetika   metabolismus   MeSH
• transkriptom fyziologie   MeSH
• transplantace ledvin škodlivé účinky   trendy   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVES: Strict BP control can retard progression of CKD in children. This prospective 3-year randomized controlled trial is aimed to investigate whether strict BP control can retard progression of chronic allograft dysfunction. METHODS: Twenty-three pediatric patients were randomly selected to the standard BP group (STAND, target 24-hour MAP 50-95th percentile, n = 11) or the intensified BP group (INTENS, target 24-hour MAP <50th percentile, n = 12). The primary endpoint was an annual reduction in eGFR (Schwartz formula, mL/min/1.73 m2 /y), secondary graft survival, BP, proteinuria, and safety. RESULTS: A total of 21 children (age at entry 11.2 (range 6.2-16.8) years) completed the study, with 73% of children in INTENS and 70% of children in STAND group reached their goal BP. Ambulatory indexed 24-hour MAP decreased significantly in INTENS group (from 0.94 (range 0.86-1.17) to 0.85 (range 0.79-1.01, P < 0.01)) but not in STAND group (from 0.93 (range 0.85-1.07) to 0.90 (range 0.84-1.01)). Proteinuria did not change significantly in either group (22.1 mg/mmol creatinine to 15.3 in STAND group vs 25.7 to 11.8 in INTENS group). The annual reduction in eGFR did not differ between the INTENS and STAND groups (-1.9 mL/min/1.73 m2 /y (range +6.4 to -14.3) vs -0.9 (range +4.0 to -8.5)). CONCLUSION: This first randomized controlled trial on strict BP control has demonstrated that strict BP control is feasible in 73% of children but the strict BP control does not lead to retardation of graft function decline in comparison with standard BP control. However, the results need to be interpreted with caution keeping the major limitation of the study, that is, small sample size in mind.

• MeSH
• ambulantní monitorování krevního tlaku MeSH
• antihypertenziva terapeutické užití   MeSH
• chronické selhání ledvin patofyziologie   chirurgie   MeSH
• dítě MeSH
• hypertenze diagnóza   etiologie   prevence a kontrola   MeSH
• lidé MeSH
• mladiství MeSH
• pooperační komplikace diagnóza   prevence a kontrola   MeSH
• přežívání štěpu fyziologie   MeSH
• prospektivní studie MeSH
• transplantace ledvin * MeSH
• vyšetření funkce ledvin MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Cerebellar diseases causing substantial cell loss often lead to severe functional deficits and restoration of cerebellar function is difficult. Neurotransplantation therapy could become a hopeful method, but there are still many limitations and unknown aspects. Studies in a variety of cerebellar mutant mice reflecting heterogeneity of human cerebellar degenerations show promising results as well as new problems and questions to be answered. The aim of this work was to compare the development of embryonic cerebellar grafts in adult B6CBA Lurcher and B6.BR pcd mutant mice and strain-matched healthy wild type mice. Performance in the rotarod test, graft survival, structure, and volume was examined 2 months after the transplantation or sham-operation. The grafts survived in most of the mice of all types. In both B6CBA and B6.BR wild type mice and in pcd mice, colonization of the host's cerebellum was a common finding, while in Lurcher mice, the grafts showed a low tendency to infiltrate the host's cerebellar tissue. There were no significant differences in graft volume between mutant and wild type mice. Nevertheless, B6CBA mice had smaller grafts than their B6.BR counterparts. The transplantation did not improve the performance in the rotarod test. The study showed marked differences in graft integration into the host's cerebellum in two types of cerebellar mutants, suggesting disease-specific factors influencing graft fate.

• MeSH
• modely nemocí na zvířatech * MeSH
• mozeček fyziologie   transplantace   MeSH
• myši - mutanty neurologické MeSH
• myši inbrední C57BL MeSH
• myši inbrední CBA MeSH
• myši MeSH
• nemoci mozečku patologie   terapie   MeSH
• neurodegenerativní nemoci patologie   terapie   MeSH
• přežívání štěpu fyziologie   MeSH
• transplantace fetální tkáně metody   MeSH
• transplantace mozkové tkáně metody   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dárci tkání zásobování a distribuce   MeSH
• dějiny 21. století MeSH
• histokompatibilita genetika   MeSH
• imunogenetika dějiny   metody   trendy   MeSH
• imunologická tolerance * MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé MeSH
• přežívání štěpu fyziologie   MeSH
• rejekce štěpu diagnóza   genetika   imunologie   prevence a kontrola   MeSH
• testování histokompatibility MeSH
• transplantace hematopoetických kmenových buněk metody   MeSH
• transplantace orgánů metody   MeSH
• Check Tag
• dějiny 21. století MeSH
• lidé MeSH
• Publikační typ
• historické články MeSH
• kongresy MeSH
• Geografické názvy
• Česká republika MeSH

For many degenerative cerebellar diseases, currently, no effective treatment that would substantially restore cerebellar functions is available. Neurotransplantation could be a promising therapy for such cases. Nevertheless, there are still severe limitations for routine clinical use. The aim of the work was to assess volume and morphology and functional impact on motor skills of an embryonic cerebellar graft injected in the form of cell suspension in Lurcher mutant and wild-type mice of the B6CBA and C3H strains after a 6-month survival period. The grafts survived in the majority of the mice. In both B6CBA and C3H Lurcher mice, most of the grafts were strictly delimited with no tendency to invade the host cerebellum, while in wild-type mice, graft-derived Purkinje cells colonized the host's cerebellum. In C3H Lurcher mice, but not in B6CBA Lurchers, the grafts had smaller volume than in their wild-type counterparts. C3H wild-type mice had significantly larger grafts than B6CBA wild-type mice. No positive effect of the transplantation on performance in the rotarod test was observed. The findings suggest that the niche of the Lurcher mutant cerebellum has a negative impact on integration of grafted cells. This factor seems to be limiting for specific functional effects of the transplantation therapy in this mouse model of cerebellar degeneration.

• MeSH
• druhová specificita MeSH
• longitudinální studie MeSH
• metoda rotující tyčky MeSH
• modely nemocí na zvířatech MeSH
• motorické dovednosti MeSH
• mozeček embryologie   patologie   transplantace   MeSH
• myši - mutanty neurologické MeSH
• myši inbrední C3H MeSH
• myši inbrední CBA MeSH
• myši transgenní MeSH
• nemoci mozečku patologie   patofyziologie   terapie   MeSH
• neurodegenerativní nemoci patologie   patofyziologie   terapie   MeSH
• přežívání štěpu * fyziologie   MeSH
• transplantace mozkové tkáně * MeSH
• zelené fluorescenční proteiny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Renal transplantation is associated with a large number of risk factors that can have an influence on early renal graft function (ERGF). One of these factors could be the increasing number of obese kidney donors. The mechanisms of reduced ERGF in obese kidney donors are still poorly understood. To that end, we compared ERGF in recipients with body mass index (BMI), perivascular fat and plasma inflammation markers of live kidney donors. We hypothesized that the BMI of donors would negatively correlate with an average increase of glomerular filtration rate (GFR) and that it would also be associated with increased perivascular and plasma inflammation markers in the first seven days after transplantation. Between January 2013 and December 2014, some 58 living kidney transplantation pairs were included in the study. Donor and recipient demographic data, preoperative BMI, blood C-reactive protein (CRP) and adiponectin levels, perivascular adipose tissue (PAT) samples and recipient blood creatinine levels were analyzed. The median CRP of donors was 0.68 mg/l (max: 8.66 mg/l, min: 0.33 mg/l), the median of M1 macrophages (CD14+CD16+) in one gram of PAT was 5940 (max: 41 100, min: 248) and the median of adiponectin was 411 930 pg/ml (max: 14 217 000, min: 167 300) in plasma. We did not find any association between early renal graft function and the percentage of M1 macrophages in donor perirenal adipose tissue (p=0.83, r=0.03, n=58), adiponectin (p=0.65, r=0.06, n=58) or CRP (p=0.16, r=0.2, n=58) in plasma. The obesity level of donors, expressed as BMI, did not correlate with early renal graft function in the first seven days after transplantation. The associations between ERGF and plasma and perivascular fat inflammation markers were not significant. We confirmed a negative correlation between the BMI of recipients and an average increase of GFR in the first seven days after transplantation (p<0.02, r=-0.325, N=58). We confirmed a negative correlation of adiponectin plasma concentration to the BMI of donors.

• MeSH
• dospělí MeSH
• dyslipidemie epidemiologie   metabolismus   MeSH
• hodnoty glomerulární filtrace fyziologie   MeSH
• hypertenze epidemiologie   metabolismus   MeSH
• index tělesné hmotnosti * MeSH
• lidé středního věku MeSH
• lidé MeSH
• přežívání štěpu fyziologie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• transplantace ledvin škodlivé účinky   trendy   MeSH
• tuková tkáň metabolismus   MeSH
• výsledek terapie MeSH
• žijící dárci * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH