Human umbilical cord-derived mesenchymal stem cells conditioned medium attenuate interstitial fibrosis and stimulate the repair of tubular epithelial cells in an irreversible model of unilateral ureteral obstruction

被引:38
作者
Liu, Bo [1 ,3 ]
Ding, Feng-Xia [2 ,3 ]
Liu, Yang [1 ,3 ]
Xiong, Geng [1 ]
Lin, Tao [1 ]
He, Da-Wei [1 ]
Zhang, Yuan-Yuan [4 ]
Zhang, De-Ying [1 ,3 ]
Wei, Guang-Hui [1 ]
机构
[1] Chongqing Med Univ, Dept Urol, Childrens Hosp, 136,Zhongshan 2, Chongqing 400014, Peoples R China
[2] Chongqing Int Sci & Technol Cooperat Ctr Child De, Dept Resp Med, Chongqing, Peoples R China
[3] Chongqing Int Sci & Technol Cooperat Ctr Child De, Minist Educ, Key Lab Child Dev & Disorders, Chongqing Key Lab Pediat, Chongqing, Peoples R China
[4] Wake Forest Sch Med, Wake Forest Inst Regenerat Med, Winston Salem, NC USA
基金
中国国家自然科学基金;
关键词
Fibrosis; Mesenchymal stem cells; Repair; Unilateral ureteral obstruction; KIDNEY FIBROSIS; STROMAL CELLS; NEPHROPATHY; PROTECTS; INJURY;
D O I
10.1111/nep.13099
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
AimThe growing number of patients suffering from chronic renal disease (CKD) is a challenge for the development of innovative therapies. Researchers have studied the therapeutic effects of cell therapy in acute kidney injury (AKI). However, the therapeutic effect of conditional medium (CM) in the CKD models have been rarely reported. Here, we examined the effects of umbilical cord derived-mesenchymal stem cells (hUC-MSCs) CM on renal fibrosis in a rat model of unilateral ureteral obstruction (UUO). MethodsAnimals were randomly divided into three groups: sham-operated, UUO, UUO + CM. CM was administered via the left renal artery after total ligation of the left ureter. Rats were killed after 14 days of obstruction. Histological changes and oxidative stress parameters were assessed. Western blotting and immunohistochemistry analysis were used to measure epithelial-mesenchymal transition (EMT) markers, including epithelial cadherin (E-cadherin), -smooth muscle actin (-SMA), tumour necrosis factor- (TNF-), Collagen-I, and transforming growth factor 1 (TGF-1). Proliferation and apoptosis of renal tubular epithelial cells (RTEs) were also measured. ResultsHucMSC-CM significantly reduced the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), and increased the activity of glutathione (GSH) induced by UUO. Moreover, CM significantly reduced the expression of TGF-1, -SMA, TNF- and Collagen-I in UUO kidney, promoted the proliferation of RTEs and inhibited its apoptosis. In addition, the increased expression of E-cadherin also reflects the effective improvement of renal interstitial fibrosis. ConclusionThis study shows that CM protects UUO-induced kidney damage and therefore could be a potential tool to prevent CKD progression. Summary at a Glance This paper reports the renoprotective effects of conditioned media (CM) from umbilical cord derived-mesenchymal stem cells using a model of unilateral ureteral obstruction in rats. A variety of indicators of fibrosis were reduced following the administration of CM, together with the concurrent reduction in oxidative stress and increased antioxidant enzymes.
引用
收藏
页码:728 / 736
页数:9
相关论文
共 28 条
[1]   Arterially Delivered Mesenchymal Stem Cells Prevent Obstruction-Induced Renal Fibrosis [J].
Asanuma, Hiroshi ;
Vanderbrink, Brian A. ;
Campbell, Matthew T. ;
Hile, Karen L. ;
Zhang, Hongji ;
Meldrum, Daniel R. ;
Meldrum, Kirstan K. .
JOURNAL OF SURGICAL RESEARCH, 2011, 168 (01) :E51-E59
[2]   Stromal cells protect against acute tubular injury via an endocrine effect [J].
Bi, Baoyuan ;
Schmitt, Roland ;
Israilova, Malika ;
Nishio, Hitoshi ;
Cantley, Lloyd G. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 18 (09) :2486-2496
[3]   Mesenchymal Stem Cell-Derived Microvesicles Protect Against Acute Tubular Injury [J].
Bruno, Stefania ;
Grange, Cristina ;
Deregibus, Maria Chiara ;
Calogero, Raffaele A. ;
Saviozzi, Silvia ;
Collino, Federica ;
Morando, Laura ;
Busca, Alessandro ;
Falda, Michele ;
Bussolati, Benedetta ;
Tetta, Ciro ;
Camussi, Giovanni .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 20 (05) :1053-1067
[4]   Mesenchymal Stem Cell Conditioned Medium Promotes Proliferation and Migration of Alveolar Epithelial Cells under Septic Conditions In Vitro via the JNK-P38 Signaling Pathway [J].
Chen, Jie ;
Li, Yanqin ;
Hao, Haojie ;
Li, Chonghui ;
Du, Yu ;
Hu, Ye ;
Li, Jian ;
Liang, Zhixin ;
Li, Chunsun ;
Liu, Jiejie ;
Chen, Liangan .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2015, 37 (05) :1830-1846
[5]   Leonurine ameliorates kidney fibrosis via suppressing TGF-β and NF-κB signaling pathway in UUO mice [J].
Cheng, Haibo ;
Bo, Yun ;
Shen, Weixing ;
Tan, Jiani ;
Jia, Zhirong ;
Xu, Changliang ;
Li, Furong .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2015, 25 (02) :406-415
[6]   Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Medium Attenuate Fibrosis in an Irreversible Model of Unilateral Ureteral Obstruction [J].
da Silva, Andrei F. ;
Silva, Kleiton ;
Reis, Luciana A. ;
Teixeira, Vicente P. C. ;
Schor, Nestor .
CELL TRANSPLANTATION, 2015, 24 (12) :2657-2666
[7]   Notch-3 receptor activation drives inflammation and fibrosis following tubulointerstitial kidney injury [J].
Djudjaj, Sonja ;
Chatziantoniou, Christos ;
Raffetseder, Ute ;
Guerrot, Dominique ;
Dussaule, Jean-Claude ;
Boor, Peter ;
Kerroch, Monique ;
Hanssen, Lydia ;
Brandt, Sabine ;
Dittrich, Annemarie ;
Ostendorf, Tammo ;
Floege, Juergen ;
Zhu, Cheng ;
Lindenmeyer, Maja ;
Cohen, Clemens D. ;
Mertens, Peter R. .
JOURNAL OF PATHOLOGY, 2012, 228 (03) :286-299
[8]   Evidence that inhibition of tubular cell apoptosis protects against renal damage and development of fibrosis following ureteric obstruction [J].
Docherty, NG ;
O'Sullivan, OE ;
Healy, DA ;
Fitzpatrick, JM ;
Watson, RWG .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2006, 290 (01) :F4-F13
[9]   Growth factors and renal regeneration [J].
Flaquer, M. ;
Romagnani, P. ;
Cruzado, J. M. .
NEFROLOGIA, 2010, 30 (04) :385-393
[10]  
Gatti S., 2011, NEPHROL DIAL TRANSPL, P1