Polina Ermakova

Islet allotransplantation offers a promising cell therapy for type 1 diabetes, but challenges such as limited donor availability and immunosuppression persist. Microencapsulation of islets in polymer-coated alginate microcapsules is a favored strategy for immune protection and maintaining islet viability. This study introduces Poly [2-(methacryloyloxy)ethyl]trimethylammonium chloride (PMETAC) as an innovative coating material for microcapsules. PMETAC enhances biocompatibility and durability, marking a significant advancement in islet encapsulation. Our approach combines alginate with PMETAC to create Langerhans islet microcapsules, simplifying material composition and preparation and ultimately lowering costs and increasing clinical applicability. Our comprehensive evaluation of the stability (including osmotic stability, thermal stability, and culture condition stability) and cytotoxicity of a novel microencapsulation system based on alginate-PMETAC-alginate offers insights into its potential application in islet immunoisolation strategies. Microcapsules with PMETAC content ranging from 0.01 to 1% are explored in the current work. The results indicate that the coatings made with 0.4% PMETAC show the most promising outcomes, remaining stable in the mentioned tests and exhibiting the required permeability. It was shown that the islets encapsulated in this manner retain viability and functional activity. Thus, alginate microcapsules coated with 0.4% PMETAC are suitable for further animal trials. While our findings are promising, further studies, including animal testing, will be necessary to evaluate the clinical applicability of our encapsulation method.

A decrease in the regenerative potential of the liver during the development of non-alcoholic fatty liver disease (NAFLD), which is observed in the vast majority of patients with diabetes mellitus type 1, significantly increases the risk of postoperative liver failure. In this regard, it is necessary to develop new approaches for the rapid intraoperative assessment of the condition of liver tissue in the presence of concomitant liver pathology. A modern label-free approach based on multiphoton microscopy, second harmonic generation (SHG), and fluorescence lifetime imaging microscopy (FLIM) allow for the evaluation of the structure of liver tissue as well as the assessment of the metabolic state of hepatocytes, even at the cellular level. We obtained optical criteria and identified specific changes in the metabolic state of hepatocytes for a reduced liver regenerative potential in the presence of induced diabetes mellitus type 1. The obtained criteria will expand the possibilities for the express assessment of the structural and functional state of liver tissue in clinical practice.

was to assess the effectiveness of total pancreatectomy followed by restoration of glucose tolerance in treatment of patients with chronic genetically determined pain pancreatitis. Materials and Methods: genetic mutations were examined and underwent surgical total pancreatectomy. Islets were isolated from the excised glands and implanted into the liver. Postoperative followup included an assessment of quality of life and pain intensity based on questionnaires, as well as determination of the glycemic level. Results: Following total pancreatoduodenectomy and autotransplantation, a significant decrease in pain and an improvement in quality of life were noted. Transplanted islets' function was reduced, due to their insufficient number, which required administration of exogenous insulin. Conclusion: The described experience demonstrates the TPIAT effectiveness in treatment of chronic pancreatitis, which can become a basis for further research and introduction of the technique into domestic clinical practice.

The review includes the results of analytical research on the problem of application of pancreatic islet encapsulation technologies for compensation of type 1 diabetes. We present a review of modern encapsulation technologies, approaches to encapsulation strategies, insulin replacement technologies: auto-, allo- and xenotransplantation; prospects for cell therapy for insulin-dependent conditions; modern approaches to β-cell encapsulation, possibilities of optimization of encapsulation biomaterials to increase survival of transplanted cells and reduce adverse consequences for the recipient. The main problems that need to be solved for effective transplantation of encapsulated islets of Langerhans are identified and the main strategies for translating the islet encapsulation technology into medical reality are outlined.

BACKGROUND/OBJECTIVES: This study focuses on the development and evaluation of novel alginate-poly[2-(methacryloyloxy)ethyl]trimethylammonium chloride (PMETAC) microcapsules for encapsulating pancreatic islets to address insulin deficiency in diabetes. METHODS: In previous research, we fabricated and characterized PMETAC microcapsules, evaluating their stability and permeability in vitro. This study further probes the capsules in vivo, focusing on the functional activity of the encapsulated islets post-transplantation, their viability extension, and the assessment of the immunoprotective, antifibrotic properties, and biostability of the capsules. RESULTS: Rabbit-derived islets were encapsulated and transplanted into diabetic rats. The encapsulated islets maintained insulin secretion for up to 90 days, significantly longer than non-encapsulated ones, which ceased functioning after 7 days. Histological analysis demonstrated high biocompatibility of the PMETAC coating, resulting in minimal fibrotic overgrowth around the capsules. CONCLUSIONS: The study highlights the critical role of immunoprotection and the tendency to reduce fibrosis in prolonging islet function. These findings suggest that PMETAC-coated capsules offer a promising solution for cell-based therapies in diabetes by improving graft longevity and reducing fibrotic overgrowth.