Human umbilical cord blood mesenchymal stem cell transplantation improves the
liver function of liver cirrhosis rats

doi:10.3969/j.issn.2095-4344.2013.27.010

Abstract

Abstract:

BACKGROUND: The feasibility and the mechanism of human umbilical cord blood mesenchymal stem cell transplantation for the treatment of liver cirrhosis need to be discussed in-depth.
OBJECTIVE: To observe the effect of human umbilical cord blood mesenchymal stem cell transplantation through portal vein on the liver function and tissue pathological changes of the rats with liver cirrhosis.
METHODS: Carbon tetrachloride was used to prepare rat model of liver cirrhosis. After the success of modeling, the rats in the cell transplantation group received portal vein injection of 1 mL 5-bromo-2-deoxyuridine -labeled human umbilical cord blood mesenchymal stem cells (5×106), the model group was injected with the same volume of PBS; the normal rats received 1 mL human umbilical cord blood mesenchymal stem cell transplantation via the portal vein were as the control group. At 4 weeks after transplantation, the rat tail vein blood and liver tissue were obtained for testing.
RESULTS AND CONCLUSION: At 4 weeks after cell transplantation, compared with the model group, levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin in the cell transplantation group were significantly decreased, while the albumin level was increased significantly (P < 0.01); the liver cell inflammatory necrosis, steatosis and liver fibrosis were improved significantly (P < 0.05 or P < 0.01). Immunohistochemistry and immunofluorescence staining showed that human umbilical cord blood mesenchymal stem cell colonization could be seen in the rat liver tissues of the cell transplantation group and control group, but the number of 5-bromo-2-deoxyuridine-positive cells in cell transplantation group was significantly larger than that in the control group. Reverse transcription-PCR test result showed that the expressions of cytokeratin 18 and albumin mRNA could be observed in the rat liver tissue of the cell transplantation group, but no expression could be seen in the control group. It is visible that human umbilical cord mesenchymal stem cells can improve liver
function and pathological damage of liver cirrhosis rats in a certain extent, which may relate with the intrahepatic homing colonization and hepatocyte-like cell differentiation of the transplanted cells in the liver cirrhosis rats.

Key words: stem cells, stem cell transplantation, liver cirrhosis, umbilical cord blood mesenchymal stem cells, transplantation, colonization, homing, differentiation, serum albumin, fibrosis, liver function, stem cell photographs-containing paper

CLC Number:

R394.2

Liao Jin-mao, Hu Xiao-xuan, Li Zhuo-ri . Human umbilical cord blood mesenchymal stem cell transplantation improves the
liver function of liver cirrhosis rats[J]. Chinese Journal of Tissue Engineering Research, doi: 10.3969/j.issn.2095-4344.2013.27.010.

Figures/Tables 7

References

[1] Capla JM, Grogan RH, Callaghan MJ, et al. Diabetes impairs endothelial progenitor cell-mediated blood vessel formation in response to hypoxia. Plast Reconstr Surg. 2007;119(1):59-70.

[2] Danet GH, Luongo JL, Butler G, et al. C1qRp defines a new human stem cell population with hematopoietic and hepatic potential. Proc Natl Acad Sci U S A. 2002;99(16):10441- 10445.

[3] Hong SH, Gang EJ, Jeong JA, et al. In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells.Biochem Biophys Res Commun. 2005;330(4):1153-1161.

[4] 陈海鸥,胡小宣,刘红娟,等.脐血干细胞移植治疗肝硬化的疗效观察[J].中华肝脏病杂志,2010,18(7):537-538.

[5] Jung KH, Shin HP, Lee S, et al. Effect of human umbilical cord blood-derived mesenchymal stem cells in a cirrhotic rat model. Liver Int. 2009;29(6):898-909.

[6] 金光鑫,吴德全.脐带血间充质干细胞研究进展[J].国际移植与血液净化杂志,2006,4(5):45-48.

[7] Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells. 2003;21(1):105-110.

[8] Jonker AM, Dijkhuis FW, Boes A, et al. Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats. Hepatology. 1992;15(3):423-431.

[9] Jonker AM, Dijkhuis FW, Kroese FG, et al. Immunopathology of acute galactosamine hepatitis in rats. Hepatology. 1990; 11(4):622-627.

[10] Yan L, Xu SP, Wang SZ, et al. G-CSF mobilized PBMCs contribute to the liver function of cirrhotic rats. Excli J. 2010; 9:67-75.

[11] Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells.The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-317.

[12] Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418(6893):41-49.

[13] Yang CC, Shih YH, Ko MH, et al. Transplantation of human umbilical mesenchymal stem cells from Wharton's jelly after complete transection of the rat spinal cord. PLoS One. 2008; 3(10):e3336.

[14] Chao KC, Chao KF, Fu YS, et al. Islet-like clusters derived from mesenchymal stem cells in Wharton's Jelly of the human umbilical cord for transplantation to control type 1 diabetes. PLoS One.2008;3(1):e1451.

[15] Moodley Y, Atienza D, Manuelpillai U, et al. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol. 2009;175(1): 303-313.

[16] Prasanna SJ, Gopalakrishnan D, Shankar SR, et al. Pro-inflammatory cytokines, IFNgamma and TNFalpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PLoS One. 2010;5(2):e9016.

[17] Liu Y, Mu R, Wang S, et al. Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis. Arthritis Res Ther. 2010;12(6):R210.

[18] Zhao L, Weir MD, Xu HH. Human umbilical cord stem cell encapsulation in calcium phosphate scaffolds for bone engineering. Biomaterials. 2010;31(14):3848-3857.

[19] Struys T, Moreels M, Martens W, et al. Ultrastructural and immunocytochemical analysis of multilineage differentiated human dental pulp- and umbilical cord-derived mesenchymal stem cells. Cells Tissues Organs. 2011;193(6):366-378.

[20] Chang SJ, Weng SL, Hsieh JY, et al. MicroRNA-34a modulates genes involved in cellular motility and oxidative phosphorylation in neural precursors derived from human umbilical cord mesenchymal stem cells. BMC Med Genomics. 2011;4:65.

[21] Zhao Z, Chen Z, Zhao X, et al. Sphingosine-1-phosphate promotes the differentiation of human umbilical cord mesenchymal stem cells into cardiomyocytes under the designated culturing conditions. J Biomed Sci. 2011;18:37.

[22] Tse W, Laughlin MJ. Umbilical cord blood transplantation: a new alternative option. Hematology Am Soc Hematol Educ Program. 2005:377-383.

[23] 胡荣昕,缪伟峰.肝纤维化动物模型的研究概况[J].实用肝脏病杂志,2007,10(2):133-135.

[24] Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology. 2008;134(6):1655-1669.

[25] Serrano AL, Mann CJ, Vidal B, et al. Cellular and molecular mechanisms regulating fibrosis in skeletal muscle repair and disease. Curr Top Dev Biol. 2011;96:167-201.

[26] 覃慧敏,田卫群.骨髓间充质干细胞经不同移植途径治疗终末期肝病[J].中华临床医师杂志,2011,5(21):6416-6418.

[27] Kim WH, Matsumoto K, Bessho K, et al. Growth inhibition and apoptosis in liver myofibroblasts promoted by hepatocyte growth factor leads to resolution from liver cirrhosis. Am J Pathol. 2005;166(4):1017-1028.

[28] Kakinuma S, Tanaka Y, Chinzei R, et al. Human umbilical cord blood as a source of transplantable hepatic progenitor cells. Stem Cells. 2003;21(2):217-227.