Varaa Negar, Azandeh Saeed, Khorsandi Layasadat, Bijan Nejad Darioush, Bayati Vahid, Bahreini Amin
Department of Anatomical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Iran J Basic Med Sci. 2018 Sep;21(9):928-935. doi: 10.22038/IJBMS.2018.27928.6847.
In this study, effects of encapsulated umbilical cord stem cells (UCSCs)-derived hepatocyte-like cells (HLCs) in high mannuronic alginate scaffolds was investigated on CCl-induced acute liver failure (ALF) in rats.
UCSCs were encapsulated in high mannuronic alginate scaffolds. Then the UCSCs differentiated into HLCs for treatment of CCl-induced ALF in rats. Thirty rats randomly divided into 5 groups: Intoxicated group received only CCl to induce ALF. In other groups including cell-free, UCSCs and HLCs, alginate scaffolds were transplanted into the liver 4 days after CCl injection. Biochemical markers including albumin (ALB), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated. Histological changes and gene expression of ALB, alpha-fetoprotein (AFP), and cytokeratin 18 (CK-18) were also assessed.
Expression of CK-18 significantly increased in HLCs compared to the UCSCs in vitro. This indicates that UCSCs can effectively differentiate into the HLCs. In CCl-intoxicated group, BUN, AST and ALT levels, and histological criteria, such as infiltration of inflammatory cells, accumulation of reticulocytes, nuclear pyknosis of hepatocyte and sinusoidal dilation, significantly increased. In this group, ALB secretion significantly decreased, while AFP expression significantly increased. Both UCSCs and HLCs encapsulated in alginate scaffolds effectively attenuated biochemical tests, improved liver cytoarchitecture, increased expression of ALB and reduced AFP expression.
Finding of the present study indicated that encapsulation of UCSCs or HLCs in alginate mannuronic scaffolds effectively improve CCl-induced ALF.
本研究探讨了包裹在高甘露糖醛酸海藻酸盐支架中的脐带干细胞（UCSCs）来源的肝样细胞（HLCs）对四氯化碳诱导的大鼠急性肝衰竭（ALF）的影响。
将UCSCs包裹在高甘露糖醛酸海藻酸盐支架中。然后将分化为HLCs的UCSCs用于治疗四氯化碳诱导的大鼠急性肝衰竭。30只大鼠随机分为5组：中毒组仅接受四氯化碳诱导急性肝衰竭。在其他组，包括无细胞组、UCSCs组和HLCs组，在注射四氯化碳4天后将海藻酸盐支架移植到肝脏中。评估包括白蛋白（ALB）、血尿素氮（BUN）、谷丙转氨酶（ALT）、谷草转氨酶（AST）和碱性磷酸酶（ALP）在内的生化指标。还评估了组织学变化以及ALB、甲胎蛋白（AFP）和细胞角蛋白18（CK-18）的基因表达。
与体外培养的UCSCs相比，HLCs中CK-18的表达显著增加。这表明UCSCs能够有效地分化为HLCs。在四氯化碳中毒组中，BUN、AST和ALT水平以及组织学标准，如炎性细胞浸润、网织红细胞积聚、肝细胞核固缩和肝血窦扩张，均显著增加。在该组中，ALB分泌显著减少，而AFP表达显著增加。包裹在海藻酸盐支架中的UCSCs和HLCs均有效地减轻了生化指标，改善了肝脏细胞结构，增加了ALB的表达并降低了AFP的表达。
本研究结果表明，将UCSCs或HLCs包裹在甘露糖醛酸海藻酸盐支架中可有效改善四氯化碳诱导的急性肝衰竭。
