Protective Effect of Allogeneic Bone Marrow Derived Mesenchymal Stem Cells Transplantation on Hepatic Warm Ischemia Reperfusion Injury in Rats_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

JIN Guangxin ¹ , QIAO Pengfei ² , HU Yanhua ² , QIU Gongcai ² , GAO Feng ² ,  WU Dequan. ²

1. Department of Emergency Surgery， The First Affiliated Hospital of Harbin Medical University， Harbin 150001， Heilongjiang Province， China;;
2. Department of General Surgery， The Second Affiliated Hospital of Harbin Medical University， Harbin 150080， Heilongjiang Province， China;

Corresponding author：

WU Dequan., Email: dqwu56@163.com

Keywords：

Bone marrow derived mesenchymal stem cells; Hepatic ischemia reperfusion injury; Oxidative stress; Apoptosis; Stem cell therapy

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Objective 　To explore repair role of allogeneic bone marrow mesenchymal stem cells （BM-MSCs） transplantation on treating hepatic ischemia reperfusion injury （HIRI） in rats.
Methods 　Ten rats were executed to get BM-MSCs， then BM-MSCs were cultured in vitro and dyed by 4，6-diamidino-2-phenylindole （DAPI）. Models of 70% hepatic ischemia reperfusion injury were eatablished. Thirty two rats were randomly divided into sham operation group （Sham group）， ischemia reperfusion group （I/R group）， Vitamin C group （VC group）， and BM-MSCs group. Serum samples were analyzed for ALT and AST， and hepatic tissue were for superoxide dismutase （SOD） and malondialdehyde （MDA）. Liver sections were stain with hematoxylin and eosin （HE） for histological analysis， TUNEL staining was applied to detect hepatic apoptosis. Serum and tissues were both collected at 24 h after reperfusion.
Results 　The isolated BM-MSCs maintained vigorous growth in vitro. Specific markers for MSCs antigens CD29 and CD44 were detected by flow cytometry， but antigens CD34 and CD45 were not be detected. Models of HIRI were stable， and BM-MSCs were detected around the periportal area by DAPI staining. Compared with I/R group， levels of ALT， AST， MDA， and AI in the VC group and BM-MSCs group decreased at 24 h after reperfusion （P＜0.05）， meanwhile SOD level increased （P＜0.05）. Compared with VC group， levels of ALT， AST， MDA， and AI in the BM-MSC group decreased at 24 h after reperfusion （P＜0.05）， meanwhile SOD level increased （P＜0.05）.
Conclusion 　BM-MSCs could protect HIRI by alleviating oxidative stress and inhibiting cellular apoptosis.

Citation： JIN Guangxin,QIAO Pengfei,HU Yanhua,QIU Gongcai,GAO Feng,WU Dequan.. Protective Effect of Allogeneic Bone Marrow Derived Mesenchymal Stem Cells Transplantation on Hepatic Warm Ischemia Reperfusion Injury in Rats. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(1): 60-65. doi: Copy

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2.	Coriat R， Leconte M， Kavian N，et al. Mangafodipir protects against hepatic ischemia-reperfusion injury in mice[J]. PLoS ONE， 2011， 6(11)：e27005.
3.	Loffredo FS， Steinhauser ML， Gannon J， et al. Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair[J]. Cell Stem Cell， 2011， 8(4)：389-398.
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5.	Liu L， Cao JX， Sun B， et al. Mesenchymal stem cells inhibition of chronic ethanol-induced oxidative damage via upregulation of phosphatidylinositol-3-kinase/Akt and modulation of extracellular signal-regulated kinase 1/2 activation in PC12 cells and neurons[J]. Neuroscience， 2010， 167(4)：1115-1124.
6.	高峰，李国良，林雨佳，等. 骨髓间充质干细胞移植途径对胰岛移植物免疫排斥反应的影响[J]. 中国普通外科杂志， 2012， 21(9)：1080-1085.
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13.	Jaeschke H， Lemasters JJ. Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury[J]. Gastroenterology， 2003， 125(4)：1246-1257.
14.	Sasaki H， Matsuno T， Nakagawa K， et al. Superoxide induces hepatocyte apoptosis during the early phase of reperfusion after murine liver ischemia[J]. Transplant Proc， 1998， 30(7)：2958-2959.
15.	Seo MY， Lee SM. Protective effect of low dose of ascorbic acid on hepatobiliary function in hepatic ischemia/reperfusion in rats[J]. J Hepatol， 2002， 36(1)：72-77.
16.	霍鑫，冯金炜，刘方峰，等. pEGFP-C1/Akt体外转染骨髓间充质干细胞对后肢缺血大鼠血管生成的影响[J]. 中国普外基础与临床杂志， 2008， 15(6)：402-407.
17.	吴德全，胡彦华，高峰，等. 冻存对人脐血间充质干细胞生物学特性的影响[J]. 中国普外基础与临床杂志， 2008(1)：36-40.
18.	Pan RL， Wang P， Xiang LX， et al. Delta-like 1 serves as a new target and contributor to liver fibrosis down-regulated by mesenchymal stem cell transplantation[J]. J Biol Chem， 2011， 286(14)：12340-12348.
19.	Angoulvant D， Ivanes F， Ferrera R， et al. Mesenchymal stem cell conditioned media attenuates in vitro and ex vivo myocardial reperfusion injury[J]. J Heart Lung Transplant， 2011， 30(1)：95-102.
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21.	Banas A， Teratani T， Yamamoto Y， et al. IFATS collection：in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury[J]. Stem Cells， 2008， 26(10)：2705-2712.
22.	Parekkadan B， van Poll D， Suganuma K， et al. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure[J]. PLoS One， 2007， 2(9)：e941.
23.	Tsai PC， Fu TW， Chen YM， et al. The therapeutic potential of human umbilical mesenchymal stem cells from Wharton’s jelly in the treatment of rat liver fibrosis[J]. Liver Transpl， 2009， 15(5)：484-495.
24.	Chang YJ， Liu JW， Lin PC， et al. Mesenchymal stem cells facilitate recovery from chemically induced liver damage and decrease liver fibrosis[J]. Life Sci， 2009， 85(13-14)：517-525.
25.	Dahlke MH， Hoogduijn M， Eggenhofer E， et al. Toward MSC in solid organ transplantation：2008 position paper of the MISOT study group[J]. Transplantation， 2009， 88(5)：614-619.

1. Glantzounis GK， Salacinski HJ， Yang W， et al. The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury：a review[J]. Liver Transpl， 2005， 11(9)：1031-1047.
2. Coriat R， Leconte M， Kavian N，et al. Mangafodipir protects against hepatic ischemia-reperfusion injury in mice[J]. PLoS ONE， 2011， 6(11)：e27005.
3. Loffredo FS， Steinhauser ML， Gannon J， et al. Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair[J]. Cell Stem Cell， 2011， 8(4)：389-398.
4. Gatti S， Bruno S， Deregibus MC， et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury[J]. NephrolDial Transplant， 2011， 26(5)：1474-1483.
5. Liu L， Cao JX， Sun B， et al. Mesenchymal stem cells inhibition of chronic ethanol-induced oxidative damage via upregulation of phosphatidylinositol-3-kinase/Akt and modulation of extracellular signal-regulated kinase 1/2 activation in PC12 cells and neurons[J]. Neuroscience， 2010， 167(4)：1115-1124.
6. 高峰，李国良，林雨佳，等. 骨髓间充质干细胞移植途径对胰岛移植物免疫排斥反应的影响[J]. 中国普通外科杂志， 2012， 21(9)：1080-1085.
7. 石臣磊，秦华东，丁超. 依达拉奉对肝缺血再灌注损伤逆转作用的研究[J]. 中国普外基础与临床杂志， 2011， 18(8)：887-889.
8. Hu YH， Wu DQ， Gao F， et al. A secretory function of human insulin-producing cells in vivo[J]. Hepatobiliary Pancreat Dis Int， 2009， 8(3)：255-260.
9. Hassan-Khabbar S， Vamy M， Cottart CH， et al. Protective effectof post-ischemic treatment with trans-resveratrol on cytokineproduction and neutrophil recruitment by rat liver[J]. Biochimie，2010， 92(4)：405-410.
10. Jaeschke H. Reactive oxygen and ischemia/reperfusion injury of the liver[J]. Chem Biol Interact， 1991， 79(2)：115-136.
11. McCord JM. Oxygen-derived free radicals in postischemic tissue injury[J]. N Engl J Med， 1985， 312(3)：159-163.
12. Georgiev P， Dahm F， Graf R， et al. Blocking the path to death：anti-apoptotic molecules in ischemia/reperfusion injury of the liver[J]. Curr Pharm Des， 2006， 12(23)：2911-2921.
13. Jaeschke H， Lemasters JJ. Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury[J]. Gastroenterology， 2003， 125(4)：1246-1257.
14. Sasaki H， Matsuno T， Nakagawa K， et al. Superoxide induces hepatocyte apoptosis during the early phase of reperfusion after murine liver ischemia[J]. Transplant Proc， 1998， 30(7)：2958-2959.
15. Seo MY， Lee SM. Protective effect of low dose of ascorbic acid on hepatobiliary function in hepatic ischemia/reperfusion in rats[J]. J Hepatol， 2002， 36(1)：72-77.
16. 霍鑫，冯金炜，刘方峰，等. pEGFP-C1/Akt体外转染骨髓间充质干细胞对后肢缺血大鼠血管生成的影响[J]. 中国普外基础与临床杂志， 2008， 15(6)：402-407.
17. 吴德全，胡彦华，高峰，等. 冻存对人脐血间充质干细胞生物学特性的影响[J]. 中国普外基础与临床杂志， 2008(1)：36-40.
18. Pan RL， Wang P， Xiang LX， et al. Delta-like 1 serves as a new target and contributor to liver fibrosis down-regulated by mesenchymal stem cell transplantation[J]. J Biol Chem， 2011， 286(14)：12340-12348.
19. Angoulvant D， Ivanes F， Ferrera R， et al. Mesenchymal stem cell conditioned media attenuates in vitro and ex vivo myocardial reperfusion injury[J]. J Heart Lung Transplant， 2011， 30(1)：95-102.
20. Kuo TK， Hung SP， Chuang CH， et al. Stem cell therapy for liver disease：parameters governing the success of using bone marrow mesenchymal stem cells[J]. Gastroenterology， 2008， 134(7)：2111-2121.
21. Banas A， Teratani T， Yamamoto Y， et al. IFATS collection：in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury[J]. Stem Cells， 2008， 26(10)：2705-2712.
22. Parekkadan B， van Poll D， Suganuma K， et al. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure[J]. PLoS One， 2007， 2(9)：e941.
23. Tsai PC， Fu TW， Chen YM， et al. The therapeutic potential of human umbilical mesenchymal stem cells from Wharton’s jelly in the treatment of rat liver fibrosis[J]. Liver Transpl， 2009， 15(5)：484-495.
24. Chang YJ， Liu JW， Lin PC， et al. Mesenchymal stem cells facilitate recovery from chemically induced liver damage and decrease liver fibrosis[J]. Life Sci， 2009， 85(13-14)：517-525.
25. Dahlke MH， Hoogduijn M， Eggenhofer E， et al. Toward MSC in solid organ transplantation：2008 position paper of the MISOT study group[J]. Transplantation， 2009， 88(5)：614-619.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Protective Effect of Allogeneic Bone Marrow Derived Mesenchymal Stem Cells Transplantation on Hepatic Warm Ischemia Reperfusion Injury in Rats

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