Human umbilical cord mesenchymal stem cells alleviate cyclophosphamide-induced liver injury in rats
- Author:
- No author available
- Journal Title:
- World Chinese Journal of Digestology
- Issue:
- 33
- DOI:
- 10.11569/wcjd.v25.i33.2956
- Key Word:
- 脐带间充质干细胞;环磷酰胺;药物性肝损伤;细胞治疗;Umbilical cord-mesenchyma stem cells;Cyclophosphamide;Liver injury;Cell therapy
Abstract： AIM To assess the effect of human umbilical cord mesenchyrnal stem cells (UC-MSCs) on cyclophosphamide (CTX)-induced liver injury.METHODS UC-MSCs were isolated from the human umbilical cord.Male SD rats were randomly divided into three groups:control group,CTX group,and CTX + UC-MSC group.The CTX group and CTX + UC-MSC group were intraperitoneally injected with CTX.After that,the control group and CTX group were injected with water via the tail vein,and the CTX + UC-MSC group was injected with MSCs via the tail vein.Six rats of each group were selected randomly and sacrificed at different time points.Blood samples were taken to measure serum alanine transaminase (ALT),aspartate transaminase (AST),alkaline phosphatase (ALP),and total bilirubin (TBIL).Liver tissues were collected for biochemical assays of malondialdehyde (MDA),lipid peroxide (LPO),NO,glutathione (GSH),glutathione peroxidase (GSH-PX),and total superoxide dismutase (T-SOD).qPCR was used to test the expression of Bcl-2,Bax,and vascular endothelial growth factor (VEGF) A.Histological examination (HE straining) and immunohistochemical staining for α-smooth muscle actin (α-SMA) and Ki-67 were also performed.RESULTS Compared with the control group,the levels of ALT,AST,ALP,and TBIL were significantly higher,the SOD,GSH,and GSH-PX contents were significantly lower,MDA,LPO,and NO were significantly higher,cell apoptosis significantly increased,and the expression of VEGFA significantly decreased in the CTX group.Compared with the CTX group,the ALT,AST,ALP,and TBIL were significantly lower,the SOD,GSH,and GSH-PX contents were significantly higher,and MDA,LPO,and NO were significantly lower in the CTX + UC-MSC group (P ＜ 0.05).The expression of Bax was lower and Bcl-2 and VEGFA expression was higher in the CTX + UC-MSC group than in the CTX group (P ＜ 0.05).Pathological analysis showed that liver status was better in the CTX + UC-MSC group than in the CTX group.The α-SMA+ cells in the CTX + UC-MSC group were less than and Ki-67+ ceils were more than those in the CTX group (P ＜ 0.05).CONCLUSION UC-MSCs injected via the tail vein could alleviate CTX-induced hepatotoxicity in rats.
- [1]赵俊暕,陈乃耀,石峻,等.人脐血间充质干细胞移植对创伤性脑损伤大鼠VEGF分泌及血管新生的影响[J].2013,(4).
- [2]梁梓宇,姜海行,覃山羽,等.大鼠骨髓间充质干细胞体外诱导肝星状细胞系凋亡[J].2010,(8).
- [3]胡美迪,郭贵海.基于肝星状细胞的骨髓间充质干细胞治疗肝纤维化的研究现状[J].2010,(24).
- [4]Yasushi,Sato.Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion.[J].2005,106.
- [5]Mairead, Hayes,Gerard, Curley,John G, Laffey.Mesenchymal stem cells - a promising therapy for Acute Respiratory Distress Syndrome.[J].2012,4.
- [6]杨化超,李茂,黄文.人脐带间充质干细胞对小鼠皮肤创面愈合及VEGF表达的影响[J].2016,(5).
- [7]Sheweita, Salah A.,El-Hosseiny, Lobna S.,Nashashibi, Munther A..Protective Effects of Essential Oils as Natural Antioxidants against Hepatotoxicity Induced by Cyclophosphamide in Mice.[J].2016,(10).
- [8]Jan G, Hengstler,Marc, Brulport,Wiebke, Schormann,etc.Generation of human hepatocytes by stem cell technology: definition of the hepatocyte.[J].2005,1(1).
- [9]Thomas Wagner.Ifosfamide Clinical Pharmacokinetics[J].1994,26(6).
- [10]L G, Buchynska,I P, Nesina,N P, Yurchenko,etc.Expression of p53, p21WAF1/CIP1, p16INK4A and Ki-67 proteins in serous ovarian tumors.[J].2007,29.
- [11]de-Carvalho AC,Carvalho AB,Takiya CM,etc.Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury.[J].2008,26(5).
- [12]Techung Lee.Stem cell therapy independent of stemness[J].2012,(12).
- [13]Moignet,A.,Hasanali,Z.,Zambello,R.,etc.Cyclophosphamide as a first-line therapy in LGL leukemia[J].2014,28(5).
- [14]Fu, Jinqiu,Zhang, Haiyan,Zhuang, Yong,etc.The Role of N-Acetyltransferase 8 in Mesenchymal Stem Cell-Based Therapy for Liver Ischemia/Reperfusion Injury in Rats.[J].2014,9(7).
- [15]Biswas,A.,Fong,C.Y.,Lin,H.D.,etc.Human umbilical cord Wharton's jelly stem cells and its conditioned medium support hematopoietic stem cell expansion ex vivo[J].2012,113(2).
- [16]Bazhanov N,Prockop DJ,Reger RL,etc.Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs).[J].2010,14(9).
- [17]Sudeepta,Aggarwal.Human mesenchymal stem cells modulate allogeneic immune cell responses.[J].2005,105.
- [18]Reto M, Baertschiger,Véronique, Serre-Beinier,Philippe, Morel,etc.Fibrogenic potential of human multipotent mesenchymal stromal cells in injured liver.[J].2009,4(8).
- [19]Gaupp D.,Baddoo M.,McBride C.,etc.Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects[J].2003,100(14).
- [20]Szabo,G.,Catalano,D.,Alao,H.,etc.Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases[J].2012,56(5).
- [21]Fujita, Tomoko,Soontrapa, Kitipong,Ito, Yoshiya,etc.Hepatic Stellate Cells Relay Inflammation Signaling From Sinusoids to Parenchyma in Mouse Models of Immune-Mediated Hepatitis[J].2016,63(4).
- [22]Li,T.,Zhu,W.,Shen,L.,etc.Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis[J].2013,22(6).
- [23]Ghaedi M,Tuleuova N,Wu J,etc.Bottom-up signaling from HGF-containing surfaces promotes hepatic differentiation of mesenchymal stem cells.[J].2011,407(2).
- [24]Tsai-Turton M,Luderer U,Luong BT,etc.Cyclophosphamide-induced apoptosis in COV434 human granulosa cells involves oxidative stress and glutathione depletion.[J].2007,98(1).