Pankreatoprivní diabetes je sekundární forma se stejnou prevalencí v evropské populaci jako diabetes mellitus 1. typu. Nejčastější příčinou je chronická pankreatitida, se kterou úzce souvisí i resekční výkony. Extrémně labilní formou je diabetes po totální pankreatektomii. Tento typ diabetu je charakterizován častým výskytem hypoglykemií, a to i těžkých epizod. Účinnou prevenci vzniku diabetu je autotransplantace ostrůvků, která se provádí od roku 1980. Tato léčba efektivně brání vzniku diabetu u třetiny pacientů a u ostatních nemocných významně snižuje výskyt hypoglykemií. Pokud tento výkon nelze provést, je vhodné pacienty monitorovat pomocí senzorů a pokusit se je léčit hybridními smyčkami. V budoucnu přicházejí do úvahy také bihormonální pumpy.
Pancreaticobiliary diabetes is a secondary form with the same prevalence in the European population as type 1 diabetes mellitus. The most common cause is chronic pancreatitis, with which resection procedures are closely related. An extremely labile form is diabetes after total pancreatectomy. This type of diabetes is characterized by frequent occurrence of hypoglycemia and even severe episodes. An effective prevention of diabetes is islet autotransplantation, which has been performed since 1980. This treatment effectively prevents diabetes in one third of patients and significantly reduces the incidence of hypoglycemia in the remaining patients. If this procedure cannot be performed, it is advisable to monitor patients with sensors and try to treat them with hybrid loops.
We have recently developed a model of pancreatic islet transplantation into a decellularized pancreatic tail in rats. As the pancreatic skeletons completely lack endothelial cells, we investigated the effect of co-transplantation of mesenchymal stem cells and endothelial cells to promote revascularization. Decellularized matrix of the pancreatic tail was prepared by perfusion with Triton X-100, sodium dodecyl sulfate and DNase solution. Isolated pancreatic islets were infused into the skeletons via the splenic vein either alone, together with adipose tissue-derived mesenchymal stem cells (adMSCs), or with a combination of adMSCs and rat endothelial cells (rat ECs). Repopulated skeletons were transplanted into the subcutaneous tissue and explanted 9 days later for histological examination. Possible immunomodulatory effects of rat adMSCs on the survival of highly immunogenic green protein-expressing human ECs were also tested after their transplantation beneath the renal capsule. The immunomodulatory effects of adMSCs were also tested in vitro using the Invitrogen Click-iT EdU system. In the presence of adMSCs, the proliferation of splenocytes as a response to phytohaemagglutinin A was reduced by 47% (the stimulation index decreased from 1.7 to 0.9, P = 0.008) and the reaction to human ECs was reduced by 58% (the stimulation index decreased from 1.6 to 0.7, P = 0.03). Histological examination of the explanted skeletons seeded only with the islets showed their partial disintegration and only a rare presence of CD31-positive cells. However, skeletons seeded with a combination of islets and adMSCs showed preserved islet morphology and rich vascularity. In contrast, the addition of syngeneic rat ECs resulted in islet-cell necrosis with only few endothelial cells present. Live green fluorescence-positive endothelial cells transplanted either alone or with adMSCs were not detected beneath the renal capsule. Though the adMSCs significantly reduced in vitro proliferation stimulated by either phytohaemagglutinin A or by xenogeneic human ECs, in vivo co-transplanted adMSCs did not suppress the post-transplant immune response to xenogeneic ECs. Even in the syngeneic model, ECs co-transplantation did not lead to sufficient vascularization in the transplant area. In contrast, islet co-transplantation together with adMSCs successfully promoted the revascularization of extracellular matrix in the subcutaneous tissue.
- MeSH
- decelularizovaná extracelulární matrix MeSH
- endoteliální buňky MeSH
- fyziologická neovaskularizace * MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- Langerhansovy ostrůvky * imunologie MeSH
- lidé MeSH
- mezenchymální kmenové buňky * MeSH
- pankreas MeSH
- transplantace Langerhansových ostrůvků * metody MeSH
- transplantace mezenchymálních kmenových buněk * metody MeSH
- tuková tkáň * cytologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Diabetes mellitus je komplexné metabolické ochorenie s poškodenou sekréciou inzulínu. Štandardnou liečbou pri autoimunitnom diabete 1. typu je podávanie inzulínu v režime bazál-bolus, resp. liečba inzulínovou pumpou. Medzi ďalšie alternatívy liečby patrí transplantácia Langerhansových ostrovčekov (LO). Napriek efektívnosti, nemôže byť vykonávaná univerzálne pre nedostatok donorov a potrebu imunosupresie. Súčasné možnosti v oblasti transplantácie kmeňových buniek prinášajú alternatívu k transplantácii LO. Napriek ich terapeutickému potenciálu, klinická životaschopnosť transplantovaných kmeňových buniek predstavuje mnoho výziev vrátane maturácie, rejekcie a prežívania. Hoci sa v súčasnosti bunky transplantujú do portálnej žily v pečeni, zdá sa, že pečeňové prostredie nemusí byť vhodné pre funkciu LO a dlhodobé prežívanie nielen kadaveróznych, ale aj kmeňových buniek. Preto je dôležité zlepšiť účinnosť transplantovaných ostrovčekov vývojom biomateriálov a využitím iných miest transplantácie s lepším prežívaním graftu. V roku 2023 bola v UNLP v Košiciach v spolupráci s IKEM v Prahe vykonaná prvá úspešná alogénna transplantácia Langerhansových ostrovčekov na Slovensku.
Diabetes mellitus is a complex metabolic disease with impaired insulin secretion. The standard treatment for autoimmune type 1 diabetes is basal-bolus insulin administration or insulin pump therapy. Other treatment alternatives include transplantation of the islets of Langerhans (LO). Despite its effectiveness, it cannot be performed universally, due to the lack of donors and the need for immunosuppression. Current opportunities in stem cell transplantation provide an alternative to LO transplantation. Despite their therapeutic potential, the clinical viability of transplanted stem cells presents many challenges, including maturation, rejection and survival. Although cells are currently transplanted into the portal vein in the liver, it appears that the hepatic environment may not be suitable for LO function and long-term survival of not only cadaveric but also stem cells. Therefore, it is important to improve the efficiency of transplanted islets by developing biomaterials and using other transplantation sites with better graft survival. In 2023, the first successful allogeneic transplantation of islets of Langerhans in Slovakia was performed at UNLP in Košice in collaboration with IKEM in Prague.
- MeSH
- autologní transplantace MeSH
- buněčná a tkáňová terapie MeSH
- diabetes mellitus 1. typu komplikace terapie MeSH
- dospělí MeSH
- homologní transplantace MeSH
- imunosupresivní léčba metody MeSH
- komplikace diabetu terapie MeSH
- lidé MeSH
- transplantace kmenových buněk MeSH
- transplantace Langerhansových ostrůvků * metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Successful pancreas or islet transplantation is currently the only cure for type 1 diabetes mellitus. Since the first pancreas transplant in 1966, there have been various refinements of surgical technique along with improved immunosuppressive regimens, resulting in significantly improved outcomes, with contemporary research into graft monitoring and newer biomarkers, potentially lengthening graft survival rates further. Patients with insulin-dependent diabetes mellitus who are eligible for pancreas or islet transplantation represent a select group, the tip of the iceberg for a significant global diabetes disease burden. In the last 50 years, there have been quantum advances in alternative technologies in diabetes therapy, both experimental and translational. Further development and improved access are required to treat the larger proportion of people suffering from diabetes. Emerging stem cell therapy is still experimental whereas alternatives including automated insulin delivery systems and islet cell transplantation are already used in some countries. Whilst automated insulin delivery systems have increased in efficacy, they still do not achieve the near physiological control of blood sugar, which can be achieved by successful pancreas or islet transplantation. This state-of-the-art review provides a summary of pancreas and islet transplantation to its current place in diabetes therapy, along with alternative and future therapies, including the obstacles associated with the dissemination of these new therapies. With the advent of these modern cellular and technological advances, this review addresses the question: are we entering an era where whole organ pancreas transplantation could be replaced entirely by modern technological advances in diabetes therapy?
Chronická pankreatitída je závažný, multifaktoriálny, fibroinflamačný syndróm charakterizovaný opakovanými bolestivými exacerbáciami. Toto ochorenie má výrazný vplyv na kvalitu života pacientov, najmä z hľadiska bolesti, rozvoja diabetes mellitus a opakovaných záchvatov akútnej pankreatitídy. Autológna transplantácia Langerhansových ostrovčekov po totálnej pankreatektómii je potenciálnou možnosťou na zachovanie endogénnej sekrécie inzulínu u pacientov so závažnými, opakujúcimi sa bolestivými atakmi chronickej pankreatitídy. V našom prípade prezentujeme pacienta s chronickou pankreatitídou trpiaceho opakovanými bolestivými exacerbáciami. Pacient potreboval opakované hospitalizácie s opakovanými ERCP zákrokmi a stentážou pankreatického vývodu. Po genetickom potvrdení hereditárnej pankreatitídy a multidisciplinárnom zhodnotení bolo rozhodnuté o totálnej pankreatektómii s autotransplantáciou ostrovčekov. V tomto prípade prezentujeme prvú medzinárodnú autotransplantáciu Langerhansových ostrovčekov v Slovenskej republike.
Chronic pancreatitis with repeated painful relapses is a severe multifactorial, fibroinflammatory syndrome that significantly affects the quality of life of patients, mainly in terms of pain, development of diabetes mellitus, and repeated attacks of acute pancreatitis. Autologous islet transplantation after total pancreatectomy is a potential option in selected patients with severe, recurrent painful episodes of chronic pancreatitis. In our case, we present a patient with severe recurrent chronic pancreatitis. The patient required frequent hospitalizations with repeated stenting of the pancreatic duct. After the confirmation of a genetic mutation, the members of the multidisciplinary session decided to perform a total pancreatectomy with islet autotransplantation. In this case, we present the first international islet cell autotransplantation of Langerhans islets in Slovakia after total pancreatectomy in a patient with chronic hereditary pancreatitis.
We previously developed a deep learning-based web service (IsletNet) for an automated counting of isolated pancreatic islets. The neural network training is limited by the absent consensus on the ground truth annotations. Here, we present a platform (IsletSwipe) for an exchange of graphical opinions among experts to facilitate the consensus formation. The platform consists of a web interface and a mobile application. In a small pilot study, we demonstrate the functionalities and the use case scenarios of the platform. Nine experts from three centers validated the drawing tools, tested precision and consistency of the expert contour drawing, and evaluated user experience. Eight experts from two centers proceeded to evaluate additional images to demonstrate the following two use case scenarios. The Validation scenario involves an automated selection of images and islets for the expert scrutiny. It is scalable (more experts, images, and islets may readily be added) and can be applied to independent validation of islet contours from various sources. The Inquiry scenario serves the ground truth generating expert in seeking assistance from peers to achieve consensus on challenging cases during the preparation for IsletNet training. This scenario is limited to a small number of manually selected images and islets. The experts gained an opportunity to influence IsletNet training and to compare other experts' opinions with their own. The ground truth-generating expert obtained feedback for future IsletNet training. IsletSwipe is a suitable tool for the consensus finding. Experts from additional centers are welcome to participate.
- MeSH
- analýza přežití MeSH
- diabetes mellitus 1. typu chirurgie patofyziologie prevence a kontrola terapie MeSH
- krevní glukóza analýza MeSH
- lidé MeSH
- regulace glykemie MeSH
- transplantace Langerhansových ostrůvků dějiny metody statistika a číselné údaje MeSH
- transplantace ledvin statistika a číselné údaje MeSH
- transplantace slinivky břišní dějiny metody statistika a číselné údaje MeSH
- transplantace * dějiny metody statistika a číselné údaje MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Transplantace inzulín-produkující tkáně je metoda vyhrazená pro úzkou skupinu pacientů s labilním diabetem především 1. typu s těžkými hypoglykemiemi. Ke správné indikaci pacientů, kteří budou z transplantační léčby profitovat, je třeba využívat moderní zdravotnické pomůcky, a to především kontinuální monitoraci glukózy. U pacientů se syndromem por-šeného vnímání hypoglykemie často ani alarmy kontinuálního monitoru nezabrání těžké hypoglykemii. Tyto pacienty je vhodné odeslat do transplantačního centra ke zvážení tran-plantace pankreatu nebo Langerhansových ostrůvků. Léčba pomocí technologií by však měla vždy indikaci transplantace předcházet.
Insulin-producing tissue transplantation is a method reserved for a narrow group of patients with unstable diabetes, especially type 1 with severe hypoglycaemia. Modern medical devices, especially continuous glucose monitoring, should be used to correctly indicate patients who will benefit from the transplant treatment. In patients with impaired hypoglycaemia awareness, continuous monitor alarms often do not prevent severe hypoglycaemia. It is advisable to refer these patients to a transplant centre to consider a transplantation of the pancreas or islets of Langerhans. However, treatment with technology should always precede the indication of transplantation.
- Klíčová slova
- kontinuální monitorace glykemie,
- MeSH
- diabetes mellitus 1. typu diagnóza komplikace terapie MeSH
- dospělí MeSH
- hypoglykemie komplikace prevence a kontrola MeSH
- lidé MeSH
- selfmonitoring glykemie metody MeSH
- senioři MeSH
- transplantace Langerhansových ostrůvků * metody MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Transplantation of pancreatic islets into subcutaneous cavities in diabetic rats may be as or even more effective than transplantation into the portal vein. Identifying the optimal timing of the individual steps in this procedure is critical. METHODS: Macroporous scaffolds were placed in the subcutaneous tissue of diabetic male Lewis rats for 7 or 28 d and the healing of the tissue inside the scaffolds was monitored. A marginal syngeneic graft comprising 4 islets/g of recipient body weight was transplanted at the best timing focusing mainly on vascularization. Recipients were monitored for blood glucose levels and tolerance tests. Histological examination was performed in all implanted scaffolds. The presence of individual endocrine cells was analyzed in detail. RESULTS: Blood glucose levels remained within the physiological range in all recipients until the end of experiment as well as body weight increase. Coefficients of glucose assimilation were normal or slightly reduced with no statistically significant differences between the groups 40 and 80 d after transplantation. Histological analysis revealed round viable islets in the liver similar to those in pancreas, but alpha cells practically disappeared, whereas islets in the scaffolds formed clusters of cells surrounded by rich vascular network and the alpha cells remained partially preserved. CONCLUSIONS: Subcutaneous transplantation of pancreatic islets is considerably less invasive but comparably efficient as commonly used islet transplantation into the portal vein. In consideration of alpha and beta cell ratio, the artificial subcutaneous cavities represent a promising site for future islet transplantation therapy.
- MeSH
- experimentální diabetes mellitus * chirurgie MeSH
- krevní glukóza MeSH
- krysa rodu rattus MeSH
- Langerhansovy ostrůvky * krevní zásobení chirurgie MeSH
- potkani inbrední LEW MeSH
- subkutánní tkáň MeSH
- transplantace Langerhansových ostrůvků * metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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
