Endoteliální glykokalyx (EG) je tenká vrstva na povrchu endotelu s širokým významem pro mikrocirkulaci a metabolismus tkání. Role EG je různorodá – funguje jako ochrana endotelu proti smykovému tření, které mediuje na intracelulární struktury endoteliálních buněk, umožňuje interakci krevních elementů a endotelu, brání rozvoji nekontrolované nástěnné trombózy a nadměrnému oxidačnímu působení radikálů. K dysfunkci EG může dojít částečnou nebo úplnou ztrátou jeho složek, což má za následek zhoršení vaskulární regulace a zvýšení vaskulární permeability. Narušení nebo dysfunkce EG jsou spojeny s patologickými stavy, jako je diabetes, chronická renální insuficience, zánětlivé stavy, sepse, hypernatremie, hypervolemie a ischemicko-reperfuzní poškození. Enzymy jako hyaluronidáza a metaloproteinázy degradují komponenty EG. Poškození EG vede k uvolňování rozpadových produktů do krevního oběhu, které lze detekovat. Existují i přímé metody vizualizace EG. Díky pokrokům ve studiu EG při transplantaci ledviny lze hodnotit komplexní vztah k této oblasti a dané klinické aspekty. Do budoucna může mít zkoumání potenciálních terapeutických možností s cílem ochrany EG dopady na lepší funkci a přežívání ledvinných štěpů. Cílem práce je shrnutí současného stavu problematiky a poukázání na význam EG u transplantace ledvin.
The endothelial glycocalyx (EG) is a thin layer on the surface of the endothelium that plays an important role for microcirculation and tissue metabolism. The role of EG is diverse – it acts as a protection of the endothelium against shear stress which is mediated on the intracellular structures of endothelial cells, allows the interaction of blood elements and endothelium, prevents the formation of uncontrolled thrombosis and excessive oxidative stress by free radicals. EG dysfunction can occur with partial or complete loss of its components, resulting in impaired vascular regulation and increased vascular permeability. Disruption or dysfunction of EG has been associated with disease states such as diabetes, chronic kidney disease, inflammatory conditions, sepsis, hypernatraemia, hypervolaemia and ischaemia/reperfusion injury. Enzymes such as hyaluronidase and metalloproteinases can degrade the components of EG. Damage to EG leads to the release of breakdown products into the bloodstream which can be detected. There are also direct methods of visualization of EG. Thanks to advances in the study of EG in kidney transplantation a comprehensive relationship in this field and specific clinical aspects can be assessed. In the future exploring potential therapeutic options to protect EG may have implications for better graft function and survival. The aim of this paper is to summarize the current knowledge and to point out the importance of EG in kidney transplantation.
The corneal endothelium plays a key role in maintaining corneal transparency. Its dysfunction is currently treated with penetrating or lamellar keratoplasty. Advanced cell therapy methods seek to address the persistent global deficiency of donor corneas by enabling the renewal of the endothelial monolayer with tissue-engineered grafts. This review provides an overview of recently published literature on the preparation of endothelial grafts for transplantation derived from cadaveric corneas that have developed over the last decade (2010-2021). Factors such as the most suitable donor parameters, culture substrates and media, endothelial graft storage conditions, and transplantation methods are discussed. Despite efforts to utilize alternative cellular sources, such as induced pluripotent cells, cadaveric corneas appear to be the best source of cells for graft preparation to date. However, native endothelial cells have a limited natural proliferative capacity, and they often undergo rapid phenotype changes in ex vivo culture. This is the main reason why no culture protocol for a clinical-grade endothelial graft prepared from cadaveric corneas has been standardized so far. Currently, the most established ex vivo culture protocol involves the peel-and-digest method of cell isolation and cell culture by the dual media method, including the repeated alternation of high and low mitogenic conditions. Culture media are enriched by additional substances, such as signaling pathway (Rho-associated protein kinase, TGF-β, etc.) inhibitors, to stimulate proliferation and inhibit unwanted morphological changes, particularly the endothelial-to-mesenchymal transition. To date, this promising approach has led to the development of endothelial grafts for the first in-human clinical trial in Japan. In addition to the lack of a standard culture protocol, endothelial-specific markers are still missing to confirm the endothelial phenotype in a graft ready for clinical use. Because the corneal endothelium appears to comprise phenotypically heterogeneous populations of cells, the genomic and proteomic expression of recently proposed endothelial-specific markers, such as Cadherin-2, CD166, or SLC4A11, must be confirmed by additional studies. The preparation of endothelial grafts is still challenging today, but advances in tissue engineering and surgery over the past decade hold promise for the successful treatment of endothelial dysfunctions in more patients worldwide.
- MeSH
- antiportéry metabolismus MeSH
- endoteliální buňky transplantace MeSH
- lidé MeSH
- proteiny přenášející anionty metabolismus MeSH
- proteomika MeSH
- rohovka MeSH
- rohovkový endotel * metabolismus transplantace MeSH
- transplantace rohovky * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: The aim of our study was to assess the impact of different thawing protocols on morphological changes arising in cryopreserved human saphenous vein grafts. METHODS: The study was performed in 12 saphenous vein grafts harvested in brain death donors. Storage in the vapor phase of liquid nitrogen for 3 or 5 years followed. Two thawing protocols were tested: slow thawing in a refrigerator at temperature +4°C for 2 hr and rapid thawing-in a water bath at +37°C. Grafts were processed for scanning electron microscopy. Comparisons of continuous parameters under study between experimental groups were performed using the t-test (age, cold ischemia time, exposure to cryoprotectant, time of storage, total thawing time, mean thawing rate, morphology scoring of thawed HSVG) and the median test (HSVG length). Categorical parameters (sex and blood group) were formally tested using the chi-square test. RESULTS: All samples were evaluated according to morphological changes and scored in terms of morphologically intact endothelium, confluent endothelium with structural inhomogeneity, disruption of the intercellular contacts, separation of the endothelial cells, complete loss of the endothelium, and damage of the subendothelial layers. There is no statistically significant difference between the sample sets at the significance level of 0.05. There was no association with donors' age, sex, and time of storage. CONCLUSIONS: Human cryopreserved saphenous vein grafts in our experimental work showed no difference in terms of structural deterioration of the endothelial surface and basal membrane depending on different thawing protocols used.
- MeSH
- časové faktory MeSH
- dospělí MeSH
- endoteliální buňky účinky léků transplantace ultrastruktura MeSH
- kryoprezervace * MeSH
- kryoprotektivní látky farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- odběr tkání a orgánů MeSH
- přežití tkáně MeSH
- vena saphena účinky léků transplantace ultrastruktura MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
PURPOSE: To evaluate the outcomes of the hybrid technique of posterior lamellar keratoplasty (Descemets' membrane endothelial keratoplasty with stromal rim, DMEK-S) in eyes with multiple ocular pathologies. METHODS: A retrospective case control study of the consecutive group of all eyes with combined ocular pathologies which underwent DMEK-S keratoplasty. We evaluated the number of pre- and post-operative complications; uncorrected distance visual acuity (UDVA); corrected distance visual acuity (CDVA) and endothelial cell density (ECD). The first group (Group 1 - 100 eyes) was compared to a control group of eyes (Group 2 - 145 eyes) without combined ocular pathologies, which were operated throughout the same time period. Comparisons were made in the 12th month of the follow-up. RESULTS: Both the UDVA and the CDVA statistical values 12 months after the surgery were significantly better in Group 2. ECD was comparable in both groups. The number of complications during surgery was considerably higher in Group 1, where a certain type of complication occurred in 15 eyes (15%), while in Group 2 this complication occurred only in 9 eyes (6.2%). In Group 1 a slightly higher number of rebubbling cases (52% vs. 48.3%) occurred, as well as more than twice as many cases of primary graft failure (34% vs. 15.7%) compared to Group 2. CONCLUSION: DMEK-S - hybrid endothelial transplantation in complicated eyes in the evaluated group of patients led to a noticeable improvement of visual acuity. When compared to surgeries in uncomplicated eyes, DMEK-S results in a higher rate of postoperative complications, especially graft detachment and primary failure.
- MeSH
- Descemetova membrána chirurgie MeSH
- dospělí MeSH
- endoteliální buňky transplantace MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- oční hypertenze etiologie MeSH
- oční nemoci chirurgie MeSH
- pooperační komplikace etiologie MeSH
- přežívání štěpu MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stroma rohovky chirurgie MeSH
- studie případů a kontrol MeSH
- transplantace rohovky metody MeSH
- výsledek terapie MeSH
- zraková ostrost fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
The limitations of surgical revascularisation and pharmacological treatment in peripheral arterial occlusive disease (PAOD) are well recognized. Therapeutic options for critical leg ischemia are consequently limited to percutaneous transluminal angioplasty (PTA) or surgical revascularisation. Unfortunately, many patients with critical leg ischemia are poor candidates for either procedure. Therapeutic angiogenesis is a novel promising tool to treat these patients. Experimental and clinical and trials of gene transfer for therapeutic angiogenesis have already shown some clinical efficacy. This review is focused on gene transfer techniques in preclinical and clinical therapeutic angiogenesis, angiogenic growth factors, vectors, delivery methods and routes. The results of clinical and experimental studies, safety and side effects of gene therapy, and the perspectives of future research are also discussed.
- MeSH
- arteriální okluzní nemoci metabolismus terapie MeSH
- dolní končetina krevní zásobení MeSH
- endoteliální buňky metabolismus transplantace MeSH
- financování organizované MeSH
- fyziologická neovaskularizace MeSH
- genetická terapie trendy MeSH
- genetické vektory MeSH
- ischemie metabolismus terapie MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- modely u zvířat MeSH
- technika přenosu genů MeSH
- vaskulární endoteliální růstové faktory genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
