Correction of Cronic Liver Failure by Transplantation of Liver Cells Suspension and Cell-engineering Designs (experimental investigation)

Abstract

На экспериментальной модели хронического фиброзирующего повреждения печени (крысы-самцы породы Вистар (n=60), затравка CCl 4 , длительность эксперимента 90 суток) изучена эффективность клеточной терапии при коррекции хронической печеночной недостаточности. Выполнено 3 группы опытов: I группа (n=10)-контрольная (введение физиологического раствора); II группа (n=20)-введение в печень суспензии клеток донорской печени в дозе 8-10×10 6 клеток; III группа (n=30)-введение в печень ассоциатов клеток донорской печени и донорских мультипотентных мезенхимальных стромальных клеток костного мозга в соотношении 5:1 и в суммарной дозе 8-10×10 6 клеток на микрочастицах инъекционного гетерогенного биополимерного гидрогеля СфероГЕЛЬ (клеточно-инженерные конструкции). Установлено, что клеточная терапия во II и III группах опытов способствовала достоверно ускоренной нормализации нарушенных функций печени: к 30-м суткам вместо 90-х суток в контроле (I группа). При этом достоверные различия в темпе нормализации функциональных показателей печени во II и III группах отсутствовали. Однако гистологический анализ показал, что через 90 суток темп дефиброзирования ткани печени в III группе был существенно более выражен, чем во II группе. Полученный эффект можно объяснить тем, что разработанные клеточно-инженерные конструкции обеспечивают адекватные условия для пролонгированной жизнедеятельности трансплантированных клеток. Ключевые слова: печеночная недостаточность, клеточная терапия, клеточно-инженерные конструкции.

Proteins of allogeneic hepatocytes and pharmacological preparations for the correction of immunometabolic disorders in experimental liver pathology

“…At present, it can be argued that oxidative, immune disorders and changes in the structural and functional properties of erythrocytes -a kind of "cellular dosimeter" of the action of pathogenic factors -have an important role in damage and regeneration of liver cells by various etiological factors (Gandillet et al 2005, Liu еt al. 2009, Minasyan 2014, He et al 2017, Pretini et al 2019.…”

“…Taking into account the widespread distribution and availability of alcoholic beverages and the fact that excessive consumption of ethanol or alcohol surrogates is the main cause leading to the development of terminal stages of liver disease, it is extremely important to find out the mechanisms of influence of the liver and bone marrow stem cells, hepatocytes, and their waste products in liver pathologies, including those of alcoholic genesis (Gandillet et al 2005, Got'e et al 2013, Nutt et al 2015. At the same time, and analysis of the scientific publications reveals lack of experimental data concerning the influence of cell technologies in conditions of chronic alcohol intoxication (CAI).…”

“…The existing problems in this area that require further solution are the characteristics of a state of the introduced cells, the methods of their introduction, and determination of the number of the introduced cells (Gandillet et al 2005, Jabri et al 2018. At the same time, the mechanisms of metabolic correction of the implanted hepatocytes require further research.…”

“…In comparison with progenitor cells and stem cells, hepatocyte cultures have a very limited ability to divide, which is a serious limiting factor for their practical use, but under stressful conditions (including acute liver damage), they fall into hyperplasia and acquire the ability to actively reproduce. The given property of hepatocytes has provided the basis for their use in the processes of liver diseases recovery (Gandillet et al 2005, Jabri et al 2018, Evseeva et al 2021.…”

Almost 40 Years of Tissue Engineering in Russia: Where Are We Now?

“…Though skin tissue engineering was the first branch of tissue engineering to develop, soon it took a back seat and scientists all over the world, including Russia, switched to developing cell products for the regeneration of other tissues and organs. In the Russian Federation, scientists then worked on bone [14] and cartilage [15] equivalents and the treatment of defects and dysfunction of different organs such as the urethra [16,17], bladder [18], heart [19], central nervous system [20], liver [21], gut [22], pancreas [23], eye [24], teeth [25], hair follicle [26], etc., using implants made of different polymeric scaffolds populated with living cells (summarized in Table 3). Other techniques like transplantations of the decellularized matrix, cells or scaffolds alone, or scaffolds impregnated with active biological molecules, cells bearing modified genes or bearing gene constructs, or differentiated induced pluripotent stem cells (iPSCs), are also popular in Russia.…”