Study on Mesenchymal Stem Cells Transplantation Through The Spleen in Treatment of Acute Liver Failure in Rat_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 HANJian-ping ¹ ,  CHENZhong ²

1. Department of General Surgery, People's Hospital of Dongtai, Dongtai 224200, Jiangsu Province, China;
2. Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China;

Corresponding author：

CHENZhong, Email: chenz999@hotmail.com

Keywords：

Mesenchymal stem cells; Spleen transplantation; Acute liver failure; Sex determining region Y gene

DOI：

10.7507/1007-9424.20140162

Video：

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Objective To evaluate the therapeutic effect of transplantation of mesenchymal stem cells(MSCs) through the spleen for acute live failure in rat, and to observe migration of transplanted MSCs in vivo. Methods One male SD rat was sacrificed to collect MSCs, and MSCs were isolated, expanded, and purified by density gradient centrifugation combined with adhere culture method. The surface antigen expressions of MSCs in the fourth generation were detected by immunohistochemistry method. Twenty-four female rats were given D-galactosamine and tumor necrosis factor α(TNF-α) to establish models of acute liver failure, and then divided into experimental group and blank control group, each group enrolled 12 rats. MSCs of male rat were transplanted into the spleen of female acute liver failure rats in experimental group at 24 hours after model establishment, but rats of blank control group were injected saline(0.5 mL). After the MSCs transplantation, blood samples of rats in 2 groups were got to test levels of serum alanine aminotransferase (ALT), total bilirubin(TBIL), and albumin(ALB). PCR method was used to determine the expression of sex determining region Y gene(SRY gene), and HE staining was used to observe the pathological change of liver tissues of rats in 2 groups. Results The MSCs of the fourth generation expressed CD44 and CD29, but didn't express CD34. There were 5(41.7%) and 3 rats(25.0%) survived at 72 hours, in 1 week and 2 weeks after MSCs transplantation in experimental group and blank control group, respectively, and the survival rate was higher in experimental group(P<0.05). The expression of SRY mRNA was detected in rats of experimental group, as well as the damage of liver tissues in rats of experimental group improved. Compared with blank control group, the levels of ALT and TBIL were lower in experimental group at all time points after MSCs transplantation(P<0.05), but in 1 week and 2 weeks after MSCs transplantation, the levels of ALB in experimental group were higher(P<0.05). Conclusion MSCs can migrate to liver tissue, settle down, and exert the function of replacing hepatocyte after it has been transplanted into the spleen.

Citation： HANJian-ping, CHENZhong. Study on Mesenchymal Stem Cells Transplantation Through The Spleen in Treatment of Acute Liver Failure in Rat. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(6): 669-674. doi: 10.7507/1007-9424.20140162 Copy

1.	Fisher RA, Strom SC.Human hepatocyte transplantation:worldwide results[J].Transplantation, 2006, 82(4):441-449.
2.	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.
3.	赵瑛.SD大鼠骨髓间充质干细胞的分离培养和鉴定[J].重庆师范大学学报:自然科学版, 2008, 25(1):75-78.
4.	Gronthos S, Graves SE, Ohta S, et al.The STRO-1⁺ fraction of adult human bone marrow contains the osteogenic precursors[J].Blood, 1994, 84(12):4164-4173.
5.	Pittenger MF, Mackay AM, Beck SC, et al.Multilineage potential of adult human mesenchymal stem cells[J].Science, 1999, 284(5411):143-147.
6.	Wakitani S, Saito T, Caplan AI.Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine[J].Muscle Nerve, 1995, 18(12):1417-1426.
7.	Cho kA, Ju SY, Cho SJ, et al.Mesenchymal stem cells showed the highest potential for the regeneration of injured liver tissue compared with other subpopulations of the bone marrow[J].Cell Biol Int, 2009, 33(7):772-777.
8.	Sato Y, Araki H, kato J, et al.Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion[J].Blood, 2005, 106(2):756-763.
9.	Porada CD, Zanjani ED, Almeida-Porad G.Adult mesenchymal stem cells:a pluripotent population with multiple applications[J].Curr Stem Cell Res Ther, 2006, 1(3):365-369.
10.	kumar S, Chanda D, Ponnazhagan S.Therapeutic potential of genetically modified mesenchymal stem cells[J].Gene Ther, 2008, 15(10):711-715.
11.	kapuscinski J.DAPI:a DNA-specific fluorescent probe[J].Biotech Histochem, 1995, 70(5):220-233.
12.	Dorfman J, Duong M, Zibaitis A, et al.Myocardial tissue engineering with autologous myoblast implantation[J].J Thorac Cardiovasc Surg, 1998, 116(5):744-751.
13.	Reinecke H, Zhang M, Bartosek T, et al.Survival, integration, and differentiation of cardiomyocyte grafts:a study in normal and injured rat hearts[J].Circulation, 1999, 100(2):193-202.
14.	Reinecke H, Poppa V, Murry CE.Skeletal muscle stem cells do not transdifferentiate into cardiomyocytes after cardiac grafting[J].J Mol Cell Cardiol, 2002, 34(2):241-249.
15.	Orlic D, kajstura J, Chimenti S, et al.Transplanted adult bone marrow cells repair myocardial infarcts in mice[J].Ann N Y Acad Sci, 2001, 938:221-229.
16.	Wagers AJ, Sherwood RI, Christensen JL, et al.Little evidence for developmental plasticity of adult hematopoietic stem cells[J].Science, 2002, 297(5590):2256-2259.
17.	Min JY, Yang Y, Converso kL, et al.Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats[J].J Appl Physiol, 2002, 92(1):288-296.
18.	Yao M, Dieterle T, Hale SL, et al.Long-term outcome of fetal cell transplantation on postinfarction ventricular remodeling and function[J].J Mol Cell Cardiol, 2003, 35(6):661-670.
19.	Hatch HM, Zheng D, Jorgensen ML, et al.SDF-1alpha/CxCR4:a mechanism for hepatic oval cell activation and bone marrow stem cell recruitment to the injured liver of rats[J].Cloning Stem Cells, 2002, 4(4):339-351.
20.	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.
21.	张刚庆,高鹏,向国安,等.同种异体骨髓间质干细胞移植在大鼠肝内的定居能力[J].中国临床康复, 2006, 10(41):183-186.
22.	洪冬玲,吴燕峰,许吕宏,等.骨髓间充质干细胞在致敏小鼠体内的示踪归巢实验[J].中山大学学报:医学科学版, 2011, 32(6):708-712.
23.	kaibori M, Adachi Y, Shimo T, et al.Stimulation of liver regeneration after hepatectomy in mice by injection of bone marrow mesenchymal stem cells via the portal vein[J].Transplant Proc, 2012, 44(4):1107-1109.
24.	Lam SP, Luk JM, Man k, et al.Activation of interleukin-6-induced glycoprotein 130/signal transducer and activator of transcription 3 pathway in mesenchymal stem cells enhances hepatic differentiation, proliferation, and liver regeneration[J].Liver Transpl, 2010, 16(10):1195-1206.
25.	Liu Y, Dulchavsky DS, Gao x, et al.Wound repair by bone marrow stromal cells through growth factor production[J].J Surg Res, 2006, 136(2):336-341.
26.	Peng L, xie DY, Lin BL, et al.Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B:short-term and long-term outcomes[J].Hepatology, 2011, 54(3):820-828.
27.	Chen x, katakowski M, Li Y, et al.Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts:growth factor production[J].J Neurosci Res, 2002, 69(5):687-691.
28.	Dai LJ, Li HY, Guan Lx, et al.The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis[J].Stem Cell Res, 2009, 2(1):16-25.
29.	Cui YL, Meng MB, Tang H, et al.Recombinant human hepatocyte growth factor for liver failure[J].Contemp Clin Trials, 2008, 29(5):696-704.
30.	小池弘美.肝細胞生長因子[J].日本醫學介紹, 2002, 23(5):226-227.
31.	Liu Y, Dulchavsky DS, Gao x, et al.Wound repair by bone marrow stromal cells through growth factor production[J].J Surg Res, 2006, 136(2):336-341.

1. Fisher RA, Strom SC.Human hepatocyte transplantation:worldwide results[J].Transplantation, 2006, 82(4):441-449.
2. 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.
3. 赵瑛.SD大鼠骨髓间充质干细胞的分离培养和鉴定[J].重庆师范大学学报:自然科学版, 2008, 25(1):75-78.
4. Gronthos S, Graves SE, Ohta S, et al.The STRO-1⁺ fraction of adult human bone marrow contains the osteogenic precursors[J].Blood, 1994, 84(12):4164-4173.
5. Pittenger MF, Mackay AM, Beck SC, et al.Multilineage potential of adult human mesenchymal stem cells[J].Science, 1999, 284(5411):143-147.
6. Wakitani S, Saito T, Caplan AI.Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine[J].Muscle Nerve, 1995, 18(12):1417-1426.
7. Cho kA, Ju SY, Cho SJ, et al.Mesenchymal stem cells showed the highest potential for the regeneration of injured liver tissue compared with other subpopulations of the bone marrow[J].Cell Biol Int, 2009, 33(7):772-777.
8. Sato Y, Araki H, kato J, et al.Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion[J].Blood, 2005, 106(2):756-763.
9. Porada CD, Zanjani ED, Almeida-Porad G.Adult mesenchymal stem cells:a pluripotent population with multiple applications[J].Curr Stem Cell Res Ther, 2006, 1(3):365-369.
10. kumar S, Chanda D, Ponnazhagan S.Therapeutic potential of genetically modified mesenchymal stem cells[J].Gene Ther, 2008, 15(10):711-715.
11. kapuscinski J.DAPI:a DNA-specific fluorescent probe[J].Biotech Histochem, 1995, 70(5):220-233.
12. Dorfman J, Duong M, Zibaitis A, et al.Myocardial tissue engineering with autologous myoblast implantation[J].J Thorac Cardiovasc Surg, 1998, 116(5):744-751.
13. Reinecke H, Zhang M, Bartosek T, et al.Survival, integration, and differentiation of cardiomyocyte grafts:a study in normal and injured rat hearts[J].Circulation, 1999, 100(2):193-202.
14. Reinecke H, Poppa V, Murry CE.Skeletal muscle stem cells do not transdifferentiate into cardiomyocytes after cardiac grafting[J].J Mol Cell Cardiol, 2002, 34(2):241-249.
15. Orlic D, kajstura J, Chimenti S, et al.Transplanted adult bone marrow cells repair myocardial infarcts in mice[J].Ann N Y Acad Sci, 2001, 938:221-229.
16. Wagers AJ, Sherwood RI, Christensen JL, et al.Little evidence for developmental plasticity of adult hematopoietic stem cells[J].Science, 2002, 297(5590):2256-2259.
17. Min JY, Yang Y, Converso kL, et al.Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats[J].J Appl Physiol, 2002, 92(1):288-296.
18. Yao M, Dieterle T, Hale SL, et al.Long-term outcome of fetal cell transplantation on postinfarction ventricular remodeling and function[J].J Mol Cell Cardiol, 2003, 35(6):661-670.
19. Hatch HM, Zheng D, Jorgensen ML, et al.SDF-1alpha/CxCR4:a mechanism for hepatic oval cell activation and bone marrow stem cell recruitment to the injured liver of rats[J].Cloning Stem Cells, 2002, 4(4):339-351.
20. 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.
21. 张刚庆,高鹏,向国安,等.同种异体骨髓间质干细胞移植在大鼠肝内的定居能力[J].中国临床康复, 2006, 10(41):183-186.
22. 洪冬玲,吴燕峰,许吕宏,等.骨髓间充质干细胞在致敏小鼠体内的示踪归巢实验[J].中山大学学报:医学科学版, 2011, 32(6):708-712.
23. kaibori M, Adachi Y, Shimo T, et al.Stimulation of liver regeneration after hepatectomy in mice by injection of bone marrow mesenchymal stem cells via the portal vein[J].Transplant Proc, 2012, 44(4):1107-1109.
24. Lam SP, Luk JM, Man k, et al.Activation of interleukin-6-induced glycoprotein 130/signal transducer and activator of transcription 3 pathway in mesenchymal stem cells enhances hepatic differentiation, proliferation, and liver regeneration[J].Liver Transpl, 2010, 16(10):1195-1206.
25. Liu Y, Dulchavsky DS, Gao x, et al.Wound repair by bone marrow stromal cells through growth factor production[J].J Surg Res, 2006, 136(2):336-341.
26. Peng L, xie DY, Lin BL, et al.Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B:short-term and long-term outcomes[J].Hepatology, 2011, 54(3):820-828.
27. Chen x, katakowski M, Li Y, et al.Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts:growth factor production[J].J Neurosci Res, 2002, 69(5):687-691.
28. Dai LJ, Li HY, Guan Lx, et al.The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis[J].Stem Cell Res, 2009, 2(1):16-25.
29. Cui YL, Meng MB, Tang H, et al.Recombinant human hepatocyte growth factor for liver failure[J].Contemp Clin Trials, 2008, 29(5):696-704.
30. 小池弘美.肝細胞生長因子[J].日本醫學介紹, 2002, 23(5):226-227.
31. Liu Y, Dulchavsky DS, Gao x, et al.Wound repair by bone marrow stromal cells through growth factor production[J].J Surg Res, 2006, 136(2):336-341.

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Study on Mesenchymal Stem Cells Transplantation Through The Spleen in Treatment of Acute Liver Failure in Rat

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