Shagidulin Murat, Onishchenko Nina, Sevastianov Victor, Krasheninnikov Mikhail, Lyundup Aleksey, Nikolskaya Alla, Kryzhanovskaya Alena, Voznesenskaia Sofia, Gorelova Mariia, Perova Nadezhda, Kozlov Igor, Venediktov Artem, Piavchenko Gennadii, Gautier Sergey
Federal State Budgetary Institution "Shumakov National Medical Research Centre of Transplantology and Artificial Organs" of the Ministry of Health of the Russian Federation, 123182 Moscow, Russia.
Federal State Autonomous Educational Institution of Higher Education, "I.M. Sechenov First Moscow State Medical University" of the Ministry of Health of the Russian Federation (Sechenov University), 119435 Moscow, Russia.
Gels. 2023 Jun 1;9(6):456. doi: 10.3390/gels9060456.
Our study sought approaches for chronic liver failure (CLF) treatment and correction via cell-engineered constructs (CECs). They are built from biopolymer-based, microstructured, and collagen-containing hydrogel (BMCG). We also strove to evaluate the functional activity of BMCG in liver regeneration.
Allogeneic liver cells (namely, hepatocytes; LC) together with mesenchymal multipotent stem cells of bone marrow origin (MMSC BM; BMSCs) were adhered to our BMCG to compose implanted liver CECs. Thereafter, we investigated a model of CLF in rats receiving the implanted CECs. The CLF had been provoked by long-term exposure to carbon tetrachloride. The study comprised male Wistar rats ( = 120) randomized into 3 groups: Group 1 was a control group with the saline treatment of the hepatic parenchyma ( = 40); Group 2 received BMCG only ( = 40); and Group 3 was loaded with CECs implanted into the parenchyma of their livers ( = 40). August rats ( = 30) made up a donor population for LCs and MMSC BM to develop grafts for animals from Group 3. The study length was 90 days.
CECs were shown to affect both biochemical test values and morphological parameters in rats with CLF.
We found BMCG-derived CECs to be operational and active, with regenerative potential. Group 3 showed significant evidence of forced liver regeneration that tended to persist until the end of the study (day 90). The phenomenon is reflected by biochemical signs of hepatic functional recovery by day 30 after grafting (compared to Groups 1 and 2), whereas structural features of liver repair (necrosis prevention, missing formation of vacuoles, degenerating LC number decrease, and delay of hepatic fibrotic transformation). Such implantation of BMCG-derived CECs with allogeneic LCs and MMSC BM might represent a proper option to correct and treat CLF, as well as to maintain affected liver function in patients with liver grafting needed.
我们的研究旨在探寻通过细胞工程构建体（CEC）治疗和纠正慢性肝衰竭（CLF）的方法。这些构建体由基于生物聚合物的、具有微观结构且含胶原蛋白的水凝胶（BMCG）制成。我们还致力于评估BMCG在肝脏再生中的功能活性。
将同种异体肝细胞（即肝实质细胞；LC）与骨髓来源的间充质多能干细胞（MMSC BM；BMSCs）附着于我们的BMCG上，以构成植入性肝脏CEC。此后，我们研究了接受植入性CEC的大鼠的CLF模型。CLF是通过长期接触四氯化碳诱发的。该研究包括120只雄性Wistar大鼠，随机分为3组：第1组为对照组，对肝实质进行生理盐水处理（n = 40）；第2组仅接受BMCG（n = 40）；第3组植入CEC至其肝脏实质中（n = 40）。30只八月龄大鼠构成了LC和MMSC BM的供体群体，用于为第3组动物制备移植物。研究时长为90天。
CEC被证明会影响CLF大鼠的生化检测值和形态学参数。
我们发现源自BMCG的CEC具有活性且能发挥作用，具有再生潜力。第3组显示出明显的肝脏再生迹象，这种趋势一直持续到研究结束（第90天）。这一现象在移植后第30天通过肝功能恢复的生化指标得以体现（与第1组和第2组相比），同时还体现在肝脏修复的结构特征上（预防坏死、空泡形成缺失、变性LC数量减少以及肝纤维化转变延迟）。这种将源自BMCG的CEC与同种异体LC和MMSC BM一起植入的方法，可能是纠正和治疗CLF以及维持需要肝脏移植患者受损肝功能的合适选择。
