A Brief Analysis of Mesenchymal Stem Cells as Biological Drugs for the Treatment of Acute-on-Chronic Liver Failure (ACLF): Safety and Potency

Author(s): Ying Feng, Ai-Tong Wang, Hong-Hong Jia, Meng Zhao, Hao Yu*

Journal Name: Current Stem Cell Research & Therapy

Volume 15 , Issue 3 , 2020

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Abstract:

Acute-on-Chronic Liver Failure (ACLF) is characterized by acute exacerbation of chronic hepatitis, organ failure, high mortality, and poor prognosis. At present, the clinical methods of treatment include comprehensive treatment with medicines, artificial liver system, and Orthotopic Liver Transplantation (OLT), and of these, OLT is considered the most effective treatment for ACLF. However, it is difficult for ACLF patients to benefit from OLT due to the shortage of liver donors, high cost, unpredictable postoperative complications, and long-term use of immunosuppressive drugs; therefore, it is important to explore a new treatment option. With the development of stem cell transplantation technology in recent years, several studies have shown that treatment of ACLF with Mesenchymal Stem Cells (MSCs) leads to higher survival rates, and has good tolerance and safety rates, thereby improving the liver function and quality of life of patients; it has also become one of the popular research topics in clinical trials. This paper summarizes the current clinical interventions and treatments of ACLF, including the clinical trials, therapeutic mechanisms, and research progress on MSC application in the treatment of ACLF. The problems and challenges of the development of MSC-based therapy in the future are also discussed.

Keywords: Mesenchymal Stem Cells (MSCs), Acute-on-Chronic Liver Failure (ACLF), stem cell therapy, clinical trials, hepatitis B virus, liver transplantation.

[1]
Bernal W, Jalan R, Quaglia A, Simpson K, Wendon J, Burroughs A. Acute-on-chronic liver failure. Lancet 2015; 386(10003): 1576-87.
[http://dx.doi.org/10.1016/S0140-6736(15)00309-8] [PMID: 26423181]
[2]
Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology 2014; 60(6): 2099-108.
[http://dx.doi.org/10.1002/hep.27406] [PMID: 25164003]
[3]
Gustot T, Jalan R. Acute-on-chronic liver failure in patients with alcohol-related liver disease. J Hepatol 2019; 70(2): 319-27.
[http://dx.doi.org/10.1016/j.jhep.2018.12.008] [PMID: 30658733]
[4]
Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Lancet 2010; 376(9736): 190-201.
[http://dx.doi.org/10.1016/S0140-6736(10)60274-7] [PMID: 20638564]
[5]
Saliba F, Samuel D. Acute liver failure: current trends. J Hepatol 2013; 59(1): 6-8.
[http://dx.doi.org/10.1016/j.jhep.2013.04.001] [PMID: 23567082]
[6]
Sarin SK, Choudhury A, Sharma MK, et al. APASL ACLF Research Consortium (AARC) for APASL ACLF working Party.. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int 2019; 13(4): 353-90.
[http://dx.doi.org/10.1007/s12072-019-09946-3] [PMID: 31172417]
[7]
Gu WY, Xu BY, Zheng X, et al. Acute-on-chronic liver failure in china: Rationale for developing a patient registry and baseline characteristics. Am J Epidemiol 2018; 187(9): 1829-39.
[http://dx.doi.org/10.1093/aje/kwy083] [PMID: 29762630]
[8]
Volarevic V, Nurkovic J, Arsenijevic N, Stojkovic M. Concise review: Therapeutic potential of mesenchymal stem cells for the treatment of acute liver failure and cirrhosis. Stem Cells 2014; 32(11): 2818-23.
[http://dx.doi.org/10.1002/stem.1818] [PMID: 25154380]
[9]
Singer NG, Caplan AI. Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol 2011; 6: 457-78.
[http://dx.doi.org/10.1146/annurev-pathol-011110-130230] [PMID: 21073342]
[10]
Rabani V, Shahsavani M, Gharavi M, Piryaei A, Azhdari Z, Baharvand H. Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression. Cell Biol Int 2010; 34(6): 601-5.
[http://dx.doi.org/10.1042/CBI20090386] [PMID: 20178458]
[11]
El-Ansary M, Abdel-Aziz I, Mogawer S, et al. Phase II trial: undifferentiated versus differentiated autologous mesenchymal stem cells transplantation in Egyptian patients with HCV induced liver cirrhosis. Stem Cell Rev Rep 2012; 8(3): 972-81.
[http://dx.doi.org/10.1007/s12015-011-9322-y] [PMID: 21989829]
[12]
Shi M, Zhang Z, Xu R, et al. Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients. Stem Cells Transl Med 2012; 1(10): 725-31.
[http://dx.doi.org/10.5966/sctm.2012-0034] [PMID: 23197664]
[13]
Wang L, Li J, Liu H, et al. Pilot study of umbilical cord-derived mesenchymal stem cell transfusion in patients with primary biliary cirrhosis. J Gastroenterol Hepatol 2013; 28(Suppl. 1): 85-92.
[http://dx.doi.org/10.1111/jgh.12029] [PMID: 23855301]
[14]
Sarin SK, Choudhury A. Acute-on-chronic liver failure: terminology, mechanisms and management. Nat Rev Gastroenterol Hepatol 2016; 13(3): 131-49.
[http://dx.doi.org/10.1038/nrgastro.2015.219] [PMID: 26837712]
[15]
Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association. Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure (2018). J Clin Hepatol 2019; 35(1): 38-44. (In chinese).
[16]
Jindal A, Kumar M, Sarin SK. Management of acute hepatitis B and reactivation of hepatitis B. Liver Int 2013; 33(Suppl. 1): 164-75.
[http://dx.doi.org/10.1111/liv.12081] [PMID: 23286861]
[17]
Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Gastroenterology, Chinese Medical Association. [Clinicalguidelines on nutrition in end-stage liver disease]. Zhonghua Gan Zang Bing Za Zhi 2019; 27(5): 330-42.
[PMID: 31177656]
[18]
Forrest EH, Atkinson SR, Richardson P, et al. STOPAH Trial Management Group. Prevalent acute-on-chronic liver failure and response to corticosteroids in alcoholic hepatitis. J Hepatol 2018; 69(5): 1200-1.
[http://dx.doi.org/10.1016/j.jhep.2018.06.019] [PMID: 30150133]
[19]
Akriviadis E, Botla R, Briggs W, Han S, Reynolds T, Shakil O. Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology 2000; 119(6): 1637-48.
[http://dx.doi.org/10.1053/gast.2000.20189] [PMID: 11113085]
[20]
Tilg H, Cani PD, Mayer EA. Gut microbiome and liver diseases. Gut 2016; 65(12): 2035-44.
[http://dx.doi.org/10.1136/gutjnl-2016-312729] [PMID: 27802157]
[21]
Saha BK, Mahtab MA, Akbar SMF, et al. APASL ACLF working party. Therapeutic implications of granulocyte colony stimulating factor in patients with acute-on-chronic liver failure: increased survival and containment of liver damage. Hepatol Int 2017; 11(6): 540-6.
[http://dx.doi.org/10.1007/s12072-017-9814-1] [PMID: 28840583]
[22]
Mookerjee RP, Pavesi M, Thomsen KL, et al. CANONIC Study Investigators of the EASL-CLIF Consortium. Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure. J Hepatol 2016; 64(3): 574-82.
[http://dx.doi.org/10.1016/j.jhep.2015.10.018] [PMID: 26519600]
[23]
Liu CP, Yu ZJ. Study on L-Ornithine-L-Aspartate in the treatment of acute-on-chronic liver failure. Chinese J Hepatol 2011; 19(1): 63-4.
[24]
Nevens F, Laleman W. Artificial liver support devices as treatment option for liver failure. Best Pract Res Clin Gastroenterol 2012; 26(1): 17-26.
[http://dx.doi.org/10.1016/j.bpg.2012.01.002] [PMID: 22482522]
[25]
Nyberg SL. Bridging the gap: advances in artificial liver support. Liver Transpl 2012; 18(Suppl. 2): S10-4.
[http://dx.doi.org/10.1002/lt.23506] [PMID: 22767444]
[26]
Karvellas CJ, Subramanian RM. Current evidence for extracorporeal liver support systems in acute liver failure and acute-on-chronic liver failure. Crit Care Clin 2016; 32(3): 439-51.
[http://dx.doi.org/10.1016/j.ccc.2016.03.003] [PMID: 27339682]
[27]
Larsen FS. Artificial liver support in acute and acute-on-chronic liver failure. Curr Opin Crit Care 2019; 25(2): 187-91.
[http://dx.doi.org/10.1097/MCC.0000000000000584] [PMID: 30672818]
[28]
Finkenstedt A, Nachbaur K, Zoller H, et al. Acute-on-chronic liver failure: excellent outcomes after liver transplantation but high mortality on the wait list. Liver Transpl 2013; 19(8): 879-86.
[http://dx.doi.org/10.1002/lt.23678] [PMID: 23696006]
[29]
Sarin SK, Choudhury A. Acute-on-chronic liver failure. Curr Gastroenterol Rep 2016; 18(12): 61.
[http://dx.doi.org/10.1007/s11894-016-0535-8] [PMID: 27747458]
[30]
Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284(5411): 143-7.
[http://dx.doi.org/10.1126/science.284.5411.143] [PMID: 10102814]
[31]
Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 1976; 4(5): 267-74.
[PMID: 976387]
[32]
Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276(5309): 71-4.
[http://dx.doi.org/10.1126/science.276.5309.71] [PMID: 9082988]
[33]
Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum 2005; 52(8): 2521-9.
[http://dx.doi.org/10.1002/art.21212] [PMID: 16052568]
[34]
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): 315-7.
[http://dx.doi.org/10.1080/14653240600855905] [PMID: 16923606]
[35]
Mushahary D, Spittler A, Kasper C, Weber V, Charwat V. Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A 2018; 93(1): 19-31.
[http://dx.doi.org/10.1002/cyto.a.23242] [PMID: 29072818]
[36]
Wang S, Qu X, Zhao RC. Clinical applications of mesenchymal stem cells. J Hematol Oncol 2012; 5: 19.
[http://dx.doi.org/10.1186/1756-8722-5-19] [PMID: 22546280]
[37]
Zhao K, Liu Q. The clinical application of mesenchymal stromal cells in hematopoietic stem cell transplantation. J Hematol Oncol 2016; 9(1): 46.
[http://dx.doi.org/10.1186/s13045-016-0276-z] [PMID: 27193054]
[38]
Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363(9419): 1439-41.
[http://dx.doi.org/10.1016/S0140-6736(04)16104-7] [PMID: 15121408]
[39]
Le Blanc K, Frassoni F, Ball L, et al. Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008; 371(9624): 1579-86.
[http://dx.doi.org/10.1016/S0140-6736(08)60690-X] [PMID: 18468541]
[40]
Zhao L, Chen S, Yang P, Cao H, Li L. The role of mesenchymal stem cells in hematopoietic stem cell transplantation: prevention and treatment of graft-versus-host disease. Stem Cell Res Ther 2019; 10(1): 182.
[http://dx.doi.org/10.1186/s13287-019-1287-9] [PMID: 31227011]
[41]
Carvello M, Lightner A, Yamamoto T, Kotze PG, Spinelli A. Mesenchymal Stem Cells for Perianal Crohn’s Disease. Cells 2019; 8(7)E764
[http://dx.doi.org/10.3390/cells8070764] [PMID: 31340546]
[42]
El-Jawhari JJ, El-Sherbiny YM, Jones EA, McGonagle D. Mesenchymal stem cells, autoimmunity and rheumatoid arthritis. QJM 2014; 107(7): 505-14.
[http://dx.doi.org/10.1093/qjmed/hcu033] [PMID: 24518000]
[43]
Ghoryani M, Shariati-Sarabi Z, Tavakkol-Afshari J, Ghasemi A, Poursamimi J, Mohammadi M. Amelioration of clinical symptoms of patients with refractory rheumatoid arthritis following treatment with autologous bone marrow-derived mesenchymal stem cells: A successful clinical trial in Iran. Biomed Pharmacother 2019; 109: 1834-40.
[http://dx.doi.org/10.1016/j.biopha.2018.11.056] [PMID: 30551438]
[44]
Moreira A, Kahlenberg S, Hornsby P. Therapeutic potential of mesenchymal stem cells for diabetes. J Mol Endocrinol 2017; 59(3): R109-20.
[http://dx.doi.org/10.1530/JME-17-0117] [PMID: 28739632]
[45]
Mansoor SR, Zabihi E, Ghasemi-Kasman M. The potential use of mesenchymal stem cells for the treatment of multiple sclerosis. Life Sci 2019; 235116830
[http://dx.doi.org/10.1016/j.lfs.2019.116830] [PMID: 31487529]
[46]
Hill M, Lewis C, Riddington M, et al. Stakeholder views and attitudes towards prenatal and postnatal transplantation of fetal mesenchymal stem cells to treat Osteogenesis Imperfecta. Eur J Hum Genet 2019; 27(8): 1244-53.
[http://dx.doi.org/10.1038/s41431-019-0387-4] [PMID: 30918362]
[47]
Miao C, Lei M, Hu W, Han S, Wang Q. A brief review: the therapeutic potential of bone marrow mesenchymal stem cells in myocardial infarction. Stem Cell Res Ther 2017; 8(1): 242.
[http://dx.doi.org/10.1186/s13287-017-0697-9] [PMID: 29096705]
[48]
Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One 2010; 5(4)e10088
[http://dx.doi.org/10.1371/journal.pone.0010088] [PMID: 20436665]
[49]
Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 2005; 105(7): 2821-7.
[http://dx.doi.org/10.1182/blood-2004-09-3696] [PMID: 15591115]
[50]
Vellasamy S, Tong CK, Azhar NA, et al. Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation. Cytotherapy 2016; 18(10): 1270-83.
[http://dx.doi.org/10.1016/j.jcyt.2016.06.017] [PMID: 27543068]
[51]
Uccelli A, Moretta L, Pistoia V. Immunoregulatory function of mesenchymal stem cells. Eur J Immunol 2006; 36(10): 2566-73.
[http://dx.doi.org/10.1002/eji.200636416] [PMID: 17013987]
[52]
Deng W, Han Q, Liao L, You S, Deng H, Zhao RC. Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA Cell Biol 2005; 24(7): 458-63.
[http://dx.doi.org/10.1089/dna.2005.24.458] [PMID: 16008514]
[53]
Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 2003; 102(10): 3837-44.
[http://dx.doi.org/10.1182/blood-2003-04-1193] [PMID: 12881305]
[54]
Plumas J, Chaperot L, Richard MJ, Molens JP, Bensa JC, Favrot MC. Mesenchymal stem cells induce apoptosis of activated T cells. Leukemia 2005; 19(9): 1597-604.
[http://dx.doi.org/10.1038/sj.leu.2403871] [PMID: 16049516]
[55]
Jarvinen L, Badri L, Wettlaufer S, et al. Lung resident mesenchymal stem cells isolated from human lung allografts inhibit T cell proliferation via a soluble mediator. J Immunol 2008; 181(6): 4389-96.
[http://dx.doi.org/10.4049/jimmunol.181.6.4389] [PMID: 18768898]
[56]
Ge W, Jiang J, Arp J, Liu W, Garcia B, Wang H. Regulatory T-cell generation and kidney allograft tolerance induced by mesenchymal stem cells associated with indoleamine 2,3-dioxygenase expression. Transplantation 2010; 90(12): 1312-20.
[http://dx.doi.org/10.1097/TP.0b013e3181fed001] [PMID: 21042238]
[57]
Najib El Haddad. Mesenchymal stem cells: Immunology and therapeutic benefits. Stem Cells Clinic Res 2011; pp. 60-81.
[58]
Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood 2007; 110(10): 3499-506.
[http://dx.doi.org/10.1182/blood-2007-02-069716] [PMID: 17664353]
[59]
Cao HJ, Wang MD, Li SG, Zhu L, Zheng JH. Paracrine effect of bone marrow mesenchymal stem cells on proliferation, apoptosis, and alpha-actin-2 expression in hepatic stellate cells. Genet Mol Res 2017; 16(1)
[http://dx.doi.org/10.4238/gmr16019201] [PMID: 28362976]
[60]
Dai LJ, Li HY, Guan LX, Ritchie G, Zhou JX. The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis. Stem Cell Res (Amst) 2009; 2(1): 16-25.
[http://dx.doi.org/10.1016/j.scr.2008.07.005] [PMID: 19383405]
[61]
Eom YW, Shim KY, Baik SK. Mesenchymal stem cell therapy for liver fibrosis. Korean J Intern Med (Korean Assoc Intern Med) 2015; 30(5): 580-9.
[http://dx.doi.org/10.3904/kjim.2015.30.5.580] [PMID: 26354051]
[62]
El Baz H, Demerdash Z, Kamel M, et al. Transplant of hepatocytes, undifferentiated mesenchymal stem cells, and in vitro hepatocyte-differentiated mesenchymal stem cells in a chronic liver failure experimental model: a comparative study. Exp Clin Transplant 2018; 16(1): 81-9.
[PMID: 28585911]
[63]
Lee CW, Chen YF, Wu HH, Lee OK. Historical Perspectives and Advances in Mesenchymal Stem Cell Research for the Treatment of Liver Diseases. Gastroenterology 2018; 154(1): 46-56.
[http://dx.doi.org/10.1053/j.gastro.2017.09.049] [PMID: 29107021]
[64]
Alfaifi M, Eom YW, Newsome PN, Baik SK. Mesenchymal stromal cell therapy for liver diseases. J Hepatol 2018; 68(6): 1272-85.
[http://dx.doi.org/10.1016/j.jhep.2018.01.030] [PMID: 29425678]
[65]
Xu WX, He HL, Pan SW, et al. combination treatments of plasma exchange and umbilical cord-derived mesenchymal stem cell transplantation for patients with hepatitis b virus-related acute-on-chronic liver failure: A clinical trial in china. Stem Cells Int 2019; 20194130757
[http://dx.doi.org/10.1155/2019/4130757] [PMID: 30863450]
[66]
Zhang Z, Lin H, Shi M, et al. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol 2012; 27(Suppl. 2): 112-20.
[http://dx.doi.org/10.1111/j.1440-1746.2011.07024.x] [PMID: 22320928]
[67]
Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 2011; 11(11): 723-37.
[http://dx.doi.org/10.1038/nri3073] [PMID: 21997792]
[68]
Wynn TA, Barron L. Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis 2010; 30(3): 245-57.
[http://dx.doi.org/10.1055/s-0030-1255354] [PMID: 20665377]
[69]
Kudlik G, Hegyi B, Czibula Á, Monostori É, Buday L, Uher F. Mesenchymal stem cells promote macrophage polarization toward M2b-like cells. Exp Cell Res 2016; 348(1): 36-45.
[http://dx.doi.org/10.1016/j.yexcr.2016.08.022] [PMID: 27578361]
[70]
Elchaninov A, Fatkhudinov T, Usman N, et al. Multipotent stromal cells stimulate liver regeneration by influencing the macrophage polarization in rat. World J Hepatol 2018; 10(2): 287-96.
[http://dx.doi.org/10.4254/wjh.v10.i2.287] [PMID: 29527264]
[71]
Li YW, Zhang C, Sheng QJ, Bai H, Ding Y, Dou XG. Mesenchymal stem cells rescue acute hepatic failure by polarizing M2 macrophages. World J Gastroenterol 2017; 23(45): 7978-88.
[http://dx.doi.org/10.3748/wjg.v23.i45.7978] [PMID: 29259373]
[72]
Parekkadan B, van Poll D, Megeed Z, et al. Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells. Biochem Biophys Res Commun 2007; 363(2): 247-52.
[http://dx.doi.org/10.1016/j.bbrc.2007.05.150] [PMID: 17869217]
[73]
Akiyama K, Chen C, Wang D, et al. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell 2012; 10(5): 544-55.
[http://dx.doi.org/10.1016/j.stem.2012.03.007] [PMID: 22542159]
[74]
Yu F, Ji S, Su L, et al. Adipose-derived mesenchymal stem cells inhibit activation of hepatic stellate cells in vitro and ameliorate rat liver fibrosis in vivo. J Formos Med Assoc 2015; 114(2): 130-8.
[http://dx.doi.org/10.1016/j.jfma.2012.12.002] [PMID: 25678175]
[75]
Wang J, Bian C, Liao L, et al. Inhibition of hepatic stellate cells proliferation by mesenchymal stem cells and the possible mechanisms. Hepatol Res 2009; 39(12): 1219-28.
[http://dx.doi.org/10.1111/j.1872-034X.2009.00564.x] [PMID: 19788697]
[76]
Chen S, Xu L, Lin N, Pan W, Hu K, Xu R. Activation of Notch1 signaling by marrow-derived mesenchymal stem cells through cell-cell contact inhibits proliferation of hepatic stellate cells. Life Sci 2011; 89(25-26): 975-81.
[http://dx.doi.org/10.1016/j.lfs.2011.10.012] [PMID: 22056375]
[77]
Haldar D, Henderson NC, Hirschfield G, Newsome PN. Mesenchymal stromal cells and liver fibrosis: a complicated relationship. FASEB J 2016; 30(12): 3905-28.
[http://dx.doi.org/10.1096/fj.201600433R] [PMID: 27601441]
[78]
Higashiyama R, Inagaki Y, Hong YY, et al. Bone marrow-derived cells express matrix metalloproteinases and contribute to regression of liver fibrosis in mice. Hepatology 2007; 45(1): 213-22.
[http://dx.doi.org/10.1002/hep.21477] [PMID: 17187438]
[79]
Lin BL, Chen JF, Qiu WH, et al. Allogeneic bone marrow-derived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure: A randomized controlled trial. Hepatology 2017; 66(1): 209-19.
[http://dx.doi.org/10.1002/hep.29189] [PMID: 28370357]
[80]
Suk KT, Yoon JH, Kim MY, et al. Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: Phase 2 trial. Hepatology 2016; 64(6): 2185-97.
[http://dx.doi.org/10.1002/hep.28693] [PMID: 27339398]
[81]
Li YH, Xu Y, Wu HM, Yang J, Yang LH, Yue-Meng W. Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation in Hepatitis B Virus Related Acute-on-Chronic Liver Failure Treated with Plasma Exchange and Entecavir: a 24-Month Prospective Study. Stem Cell Rev Rep 2016; 12(6): 645-53.
[http://dx.doi.org/10.1007/s12015-016-9683-3] [PMID: 27687792]
[82]
Liang J, Zhang H, Zhao C, et al. Effects of allogeneic mesenchymal stem cell transplantation in the treatment of liver cirrhosis caused by autoimmune diseases. Int J Rheum Dis 2017; 20(9): 1219-26.
[http://dx.doi.org/10.1111/1756-185X.13015] [PMID: 28217916]
[83]
Fang XQ, Zhang JF, Song HY, et al. [Effect of umbilical cord mesenchymal stem cell transplantation on immune function and prognosis of patients with decompensated hepatitis B cirrhosis]. Zhonghua Gan Zang Bing Za Zhi 2016; 24(12): 907-10.
[PMID: 28073411]
[84]
Jang YO, Kim YJ, Baik SK, et al. Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: a pilot study. Liver Int 2014; 34(1): 33-41.
[http://dx.doi.org/10.1111/liv.12218] [PMID: 23782511]
[85]
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): 1199-205.
[http://dx.doi.org/10.1097/MEG.0b013e32832a1f6c] [PMID: 19455046]
[86]
Mohamadnejad M, Alimoghaddam K, Mohyeddin-Bonab M, et al. Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. Arch Iran Med 2007; 10(4): 459-66.
[PMID: 17903050]
[87]
Xu L, Gong Y, Wang B, et al. Randomized trial of autologous bone marrow mesenchymal stem cells transplantation for hepatitis B virus cirrhosis: regulation of Treg/Th17 cells. J Gastroenterol Hepatol 2014; 29(8): 1620-8.
[http://dx.doi.org/10.1111/jgh.12653] [PMID: 24942592]
[88]
Wang L, Han Q, Chen H, et al. Allogeneic bone marrow mesenchymal stem cell transplantation in patients with UDCA-resistant primary biliary cirrhosis. Stem Cells Dev 2014; 23(20): 2482-9.
[http://dx.doi.org/10.1089/scd.2013.0500] [PMID: 24835895]


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VOLUME: 15
ISSUE: 3
Year: 2020
Page: [202 - 210]
Pages: 9
DOI: 10.2174/1574888X15666200101124317
Price: $65

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