Autologous bone marrow stem cell transplantation for liver cirrhosis via the hepatic artery in rabbits

doi:10.3969/j.issn.2095-4344.2016.36.011

Abstract

Abstract:

BACKGROUND: How to make more transplanted bone marrow stem cells stay and differentiate in the liver is an important issue, which is also crucial for treatment of liver cirrhosis via the hepatic artery.
OBJECTIVE: To investigate the therapeutic effect of autologous bone marrow stem cell transplantation via the hepatic artery on liver cirrhosis.
METHODS: Thirty New Zealand white rabbits were equivalently randomized into normal control, stem cell transplantation and model groups. Animal models of liver cirrhosis were made in the latter two groups. Then, model rabbits in the stem cell transplantation group were subjected to autologous bone marrow stem cell transplantation via the hepatic artery. Liver function of rabbits was detected in 1, 2, 4, 8, 10 weeks after cell transplantation, and pathological detection of the liver was performed in the 10th week.
RESULTS AND CONCLUSION: At 10 weeks after cell transplantation, the liver function of the rabbits was improved significantly compared with the model group, including reduced activities of serum alanine aminotransferase, total bilirubin and aspartate aminotransferase, shortened activated partial thromboplastin time, and increased albumin level (P < 0.05). Pathological examination of the liver showed that the liver cells in the stem cell transplantation group were intact with no obvious edema and still had the structure of the pseudolobule, and compared with the model group, the degree of liver fibrosis was significantly reduced in the stem cell transplantation group. Our experimental results show that the transplantation of autologous bone marrow stem cells via the hepatic artery has a certain therapeutic effect on liver cirrhosis by increasing the body albumin content in a short time and improving the liver function.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Liver Cirrhosis, Myeloid Progenitor Cells, Stem Cell Transplantation, Hepatic Artery, Tissue Engineering

CLC Number:

R394.2

Wang Hai-fang, Liu Hong-xia, Shao Fei, Jia Bei, Zhang Sui, Zhou Jing. Autologous bone marrow stem cell transplantation for liver cirrhosis via the hepatic artery in rabbits[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(36): 5392-5397.

Figures/Tables 2

References

[1] 李小红,叶军.中医及中西医结合治疗肝硬化研究进展[J].实用中医内科杂志,2011,25(12):49-51.
[2] 范婷婷,谢渭芬.肝纤维化和肝硬化治疗进展[J].国际消化病杂志,2010,30(6):349-351.
[3] 张海苗.不同干预方法对肝硬化住院患者心理社会状况、生活质量及疗效的影响[D].长沙:中南大学,2011.
[4] 卢昆云,杨晋辉.干细胞移植治疗肝硬化的移植途径及优缺点比较[J]. 临床肝胆病杂志,2011,27(11): 1226-1228, 1232.
[5] Yao P, Zhan Y, Xu W, et al. Hepatocyte growth factor-induced proliferation of hepatic stem-like cells depends on activation of NF-kappaB. J Hepatol. 2004; 40(3):391-398.
[6] 姚鹏,詹轶群,许望翔,等.细胞生长因子在体外对大鼠肝干细胞的影响[J].中华肝脏病杂志, 2003,11(1):33-36.
[7] Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science. 1999;284(5417):1168-1170.
[8] Miyazaki M, Akiyama I, Sakaguchi M, et al. Improved conditions to induce hepatocytes from rat bone marrow cells in culture. Biochem Biophys Res Commun. 2002; 298(1):24-30.
[9] Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet. 2004;364(9429):141-148.
[10] 金博,程留芳,孙涛,等.兔四氯化碳实验性肝硬化模型的建立[J].海军总医院学报,2005,18(3):129-131.
[11] 熊全,冯吉,王军,等.3种不同途径移植骨髓间充质干细胞治疗肝硬化模型大鼠的效果比较[J]. 第三军医大学学报, 2011,33(8):804-808.
[12] Kania G, Blyszczuk P, Jochheim A, et al. Generation of glycogen- and albumin-producing hepatocyte-like cells from embryonic stem cells. Biol Chem. 2004;385(10): 943-953.
[13] 李力,滕皋军.肝细胞移植实验研究中大鼠肝细胞的冻存与复苏初探[J].中华放射学杂志,2002,36(4):369-372.
[14] Malhi H, Gupta S. Hepatocyte transplantation: new horizons and challenges. J Hepatobiliary Pancreat Surg. 2001;8(1):40-50.
[15] Avital I, Feraresso C, Aoki T, et al. Bone marrow-derived liver stem cell and mature hepatocyte engraftment in livers undergoing rejection. Surgery. 2002;132(2):384-390.
[16] Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418(6893):41-49.
[17] Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001; 410(6829):701-705.
[18] Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science. 1999;284(5417):1168-1170.
[19] Oh SH, Miyazaki M, Kouchi H, et al. Hepatocyte growth factor induces differentiation of adult rat bone marrow cells into a hepatocyte lineage in vitro. Biochem Biophys Res Commun. 2000;279(2):500-504.
[20] Zhou YM, Hu DR, Yao P, et al. Study of mouse marrow cells differentiation into a hepatocyte lineage in vitro. Zhonghua Gan Zang Bing Za Zhi. 2004;12(12):722- 725.
[21] Theise ND, Badve S, Saxena R, et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation.Hepatology. 2000; 31(1):235-240.
[22] Avital I, Inderbitzin D, Aoki T, et al. Isolation, characterization, and transplantation of bone marrow-derived hepatocyte stem cells. Biochem Biophys Res Commun. 2001;288(1):156-164.
[23] Mitchell C, Fausto N. Bone marrow-derived hepatocytes : rare but promising. Am J Pathol. 2002; 161(2):349-350.
[24] Schwartz RE, Reyes M, Koodie L, et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest. 2002; 109(10):1291-1302.
[25] Okumoto K, Saito T, Haga H, et al. Characteristics of rat bone marrow cells differentiated into a liver cell lineage and dynamics of the transplanted cells in the injured liver. J Gastroenterol. 2006;41(1):62-69.
[26] Theise ND, Badve S, Saxena R, et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology. 2000; 31(1):235-240.
[27] Cantz T, Sharma AD, Jochheim-Richter A, et al. Reevaluation of bone marrow-derived cells as a source for hepatocyte regeneration. Cell Transplant. 2004;13(6):659-666.
[28] Yannaki E, Athanasiou E, Xagorari A, et al. G-CSF-primed hematopoietic stem cells or G-CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs. Exp Hematol. 2005;33(1):108-119.
[29] 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. Gastroenterology. 2008;134(7):2111-2121.
[30] Mohamadnejad M, Namiri M, Bagheri M, et al. Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis. World J Gastroenterol. 2007; 13(24):3359-3363.
[31] Yao P, Zhan Y, Xu W, et al. Hepatocyte growth factor-induced proliferation of hepatic stem-like cells depends on activation of NF-kappaB. J Hepatol. 2004; 40(3):391-398.
[32] Kushida T, Inaba M, Hisha H, et al. Crucial role of donor-derived stromal cells in successful treatment for intractable autoimmune diseases in mrl/lpr mice by bmt via portal vein. Stem Cells. 2001;19(3):226-235.
[33] 张强,李京雨,徐力扬,等.经肝动脉骨髓干细胞移植治疗肝硬化的初步临床应用[J].中国介入影像与治疗学,2005, 2(4):261-263.
[34] 曹葆强,林继宗,钟跃思,等.自体骨髓细胞经门静脉移植治疗肝硬化与肝功能不全的临床研究[J].中华普通外科杂志, 2007,22(5):386-389.
[35] 潘兴南,沈建坤,庄岳鹏,等.自体骨髓干细胞移植治疗终末期肝病临床研究[J].南方医科大学学报,2008,28(7): 1207-1209.
[36] Terai S, Ishikawa T, Omori K, et al. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells. 2006; 24(10):2292-2298.
[37] Gordon MY, Levicar N, Pai M, et al. Characterization and clinical application of human CD34+ stem/ progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor. Stem Cells. 2006; 24(7):1822-1830.
[38] Kharaziha P, Hellström PM, Noorinayer B, et al. Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial. Eur J Gastroenterol Hepatol. 2009;21(10):1199-1205.