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Erschienen in: Journal of Gastroenterology 2/2017

08.09.2016 | Review

Status of and candidates for cell therapy in liver cirrhosis: overcoming the “point of no return” in advanced liver cirrhosis

verfasst von: Shuji Terai, Atsunori Tsuchiya

Erschienen in: Journal of Gastroenterology | Ausgabe 2/2017

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Abstract

The treatment of liver cirrhosis is currently being standardized and developed specifically to reduce activation of hepatic stellate cells (HSCs), inhibit fibrosis, increase degradation of matrix components, and reduce activated myofibroblasts. Cell therapy can be applied in the treatment of liver cirrhosis; however, the characteristic features of this therapy differ from those of other treatments because of the involvement of a living body origin and production of multiple cytokines, chemokines, matrix metalloproteinases (MMPs), and growth factors. Thus, cell therapies can potentially have multiple effects on the damaged liver, including alleviating liver cirrhosis and stimulating liver regeneration with affecting the host cells. Cell therapies initially involved autologous bone marrow cell infusion, and have recently developed to include the use of specific cells such as mesenchymal stem cells and macrophages. The associated molecular mechanisms, routes of administration, possibility of allogeneic cell therapy, and host conditions appropriate for cell therapies are now being extensively analyzed. In this review, we summarize the status and future prospects of cell therapy for liver cirrhosis.
Literatur
1.
Zurück zum Zitat Runyon BA. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013;57:1651–3.CrossRefPubMed Runyon BA. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013;57:1651–3.CrossRefPubMed
2.
Zurück zum Zitat O’Shea RS, Dasarathy S, McCullough AJ, et al. Alcoholic liver disease. Hepatology. 2010;51:307–28.CrossRefPubMed O’Shea RS, Dasarathy S, McCullough AJ, et al. Alcoholic liver disease. Hepatology. 2010;51:307–28.CrossRefPubMed
3.
Zurück zum Zitat American Association for the Study of Liver Diseases, European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014;2014(61):642–59. American Association for the Study of Liver Diseases, European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014;2014(61):642–59.
4.
Zurück zum Zitat European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53:397–417.CrossRef European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53:397–417.CrossRef
5.
Zurück zum Zitat Fukui H, Saito H, Ueno Y, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015. J Gastroenterol. 2016;51:629–50.CrossRefPubMed Fukui H, Saito H, Ueno Y, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015. J Gastroenterol. 2016;51:629–50.CrossRefPubMed
6.
Zurück zum Zitat Williams MJ, Clouston AD, Forbes SJ. Links between hepatic fibrosis, ductular reaction, and progenitor cell expansion. Gastroenterology. 2014;146:349–56.CrossRefPubMed Williams MJ, Clouston AD, Forbes SJ. Links between hepatic fibrosis, ductular reaction, and progenitor cell expansion. Gastroenterology. 2014;146:349–56.CrossRefPubMed
7.
8.
Zurück zum Zitat Tsuchiya A, Lu WY, Weinhold B, et al. Polysialic acid/neural cell adhesion molecule modulates the formation of ductular reactions in liver injury. Hepatology. 2014;60:1727–40.CrossRefPubMed Tsuchiya A, Lu WY, Weinhold B, et al. Polysialic acid/neural cell adhesion molecule modulates the formation of ductular reactions in liver injury. Hepatology. 2014;60:1727–40.CrossRefPubMed
9.
Zurück zum Zitat Kallis YN, Robson AJ, Fallowfield JA, et al. Remodelling of extracellular matrix is a requirement for the hepatic progenitor cell response. Gut. 2011;60:525–33.CrossRefPubMed Kallis YN, Robson AJ, Fallowfield JA, et al. Remodelling of extracellular matrix is a requirement for the hepatic progenitor cell response. Gut. 2011;60:525–33.CrossRefPubMed
10.
Zurück zum Zitat Thomas JA, Pope C, Wojtacha D, et al. Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function. Hepatology. 2011;53:2003–15.CrossRefPubMed Thomas JA, Pope C, Wojtacha D, et al. Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function. Hepatology. 2011;53:2003–15.CrossRefPubMed
11.
Zurück zum Zitat Sakaida I, Terai S, Yamamoto N, et al. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology. 2004;40:1304–11.CrossRefPubMed Sakaida I, Terai S, Yamamoto N, et al. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology. 2004;40:1304–11.CrossRefPubMed
12.
Zurück zum Zitat Jang JW, Choi JY, Kim YS, et al. Long-term effect of antiviral therapy on disease course after decompensation in patients with hepatitis B virus-related cirrhosis. Hepatology. 2015;61:1809–20.CrossRefPubMed Jang JW, Choi JY, Kim YS, et al. Long-term effect of antiviral therapy on disease course after decompensation in patients with hepatitis B virus-related cirrhosis. Hepatology. 2015;61:1809–20.CrossRefPubMed
13.
Zurück zum Zitat Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373:2618–28.CrossRefPubMed Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373:2618–28.CrossRefPubMed
14.
Zurück zum Zitat Forbes SJ, Gupta S, Dhawan A. Cell therapy for liver disease: From liver transplantation to cell factory. J Hepatol. 2015;62:S157–69.CrossRefPubMed Forbes SJ, Gupta S, Dhawan A. Cell therapy for liver disease: From liver transplantation to cell factory. J Hepatol. 2015;62:S157–69.CrossRefPubMed
15.
Zurück zum Zitat Merion RM, Schaubel DE, Dykstra DM, et al. The survival benefit of liver transplantation. Am J Transplant. 2005;5:307–13.CrossRefPubMed Merion RM, Schaubel DE, Dykstra DM, et al. The survival benefit of liver transplantation. Am J Transplant. 2005;5:307–13.CrossRefPubMed
18.
Zurück zum Zitat Noureddin M, Anstee QM, Loomba R. Review article: emerging anti-fibrotic therapies in the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2016;43:1109–23.CrossRefPubMed Noureddin M, Anstee QM, Loomba R. Review article: emerging anti-fibrotic therapies in the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2016;43:1109–23.CrossRefPubMed
20.
Zurück zum Zitat Rockey DC. Translating an understanding of the pathogenesis of hepatic fibrosis to novel therapies. Clin Gastroenterol Hepatol. 2013;11(224–31):e1–5. Rockey DC. Translating an understanding of the pathogenesis of hepatic fibrosis to novel therapies. Clin Gastroenterol Hepatol. 2013;11(224–31):e1–5.
21.
Zurück zum Zitat Berardis S, Dwisthi Sattwika P, Najimi M, et al. Use of mesenchymal stem cells to treat liver fibrosis: current situation and future prospects. World J Gastroenterol. 2015;21:742–58.CrossRefPubMedPubMedCentral Berardis S, Dwisthi Sattwika P, Najimi M, et al. Use of mesenchymal stem cells to treat liver fibrosis: current situation and future prospects. World J Gastroenterol. 2015;21:742–58.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Serviddio G, Bellanti F, Vendemiale G. Free radical biology for medicine: learning from nonalcoholic fatty liver disease. Free Radic Biol Med. 2013;65:952–68.CrossRefPubMed Serviddio G, Bellanti F, Vendemiale G. Free radical biology for medicine: learning from nonalcoholic fatty liver disease. Free Radic Biol Med. 2013;65:952–68.CrossRefPubMed
23.
Zurück zum Zitat Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–85.CrossRefPubMedPubMedCentral Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–85.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Paik YH, Iwaisako K, Seki E, et al. The nicotinamide adenine dinucleotide phosphate oxidase (NOX) homologues NOX1 and NOX2/gp91phox mediate hepatic fibrosis in mice. Hepatology. 2011;53:1730–41.CrossRefPubMedPubMedCentral Paik YH, Iwaisako K, Seki E, et al. The nicotinamide adenine dinucleotide phosphate oxidase (NOX) homologues NOX1 and NOX2/gp91phox mediate hepatic fibrosis in mice. Hepatology. 2011;53:1730–41.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Traber PG, Chou H, Zomer E, et al. Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease. PLoS One. 2013;8:e75361.CrossRefPubMedPubMedCentral Traber PG, Chou H, Zomer E, et al. Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease. PLoS One. 2013;8:e75361.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Granzow M, Schierwagen R, Klein S, et al. Angiotensin-II type 1 receptor-mediated Janus kinase 2 activation induces liver fibrosis. Hepatology. 2014;60:334–48.CrossRefPubMed Granzow M, Schierwagen R, Klein S, et al. Angiotensin-II type 1 receptor-mediated Janus kinase 2 activation induces liver fibrosis. Hepatology. 2014;60:334–48.CrossRefPubMed
27.
Zurück zum Zitat Rozenfeld R, Gupta A, Gagnidze K, et al. AT1R-CB1R heteromerization reveals a new mechanism for the pathogenic properties of angiotensin II. EMBO J. 2011;30:2350–63.CrossRefPubMedPubMedCentral Rozenfeld R, Gupta A, Gagnidze K, et al. AT1R-CB1R heteromerization reveals a new mechanism for the pathogenic properties of angiotensin II. EMBO J. 2011;30:2350–63.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Ueno T, Nakamura A, Nakayama H, et al. Adiponectin suppresses endoplasmic reticulum stress in nonalcoholic steatohepatitis. Exp Ther Med. 2011;2:1035–40.PubMedPubMedCentral Ueno T, Nakamura A, Nakayama H, et al. Adiponectin suppresses endoplasmic reticulum stress in nonalcoholic steatohepatitis. Exp Ther Med. 2011;2:1035–40.PubMedPubMedCentral
29.
Zurück zum Zitat Moreno M, Chaves JF, Sancho-Bru P, et al. Ghrelin attenuates hepatocellular injury and liver fibrogenesis in rodents and influences fibrosis progression in humans. Hepatology. 2010;51:974–85.CrossRefPubMed Moreno M, Chaves JF, Sancho-Bru P, et al. Ghrelin attenuates hepatocellular injury and liver fibrogenesis in rodents and influences fibrosis progression in humans. Hepatology. 2010;51:974–85.CrossRefPubMed
30.
Zurück zum Zitat Hong F, Chou H, Fiel MI, et al. Antifibrotic activity of sorafenib in experimental hepatic fibrosis: refinement of inhibitory targets, dosing, and window of efficacy in vivo. Dig Dis Sci. 2013;58:257–64.CrossRefPubMed Hong F, Chou H, Fiel MI, et al. Antifibrotic activity of sorafenib in experimental hepatic fibrosis: refinement of inhibitory targets, dosing, and window of efficacy in vivo. Dig Dis Sci. 2013;58:257–64.CrossRefPubMed
31.
Zurück zum Zitat Choi SS, Sicklick JK, Ma Q, et al. Sustained activation of Rac 1 in hepatic stellate cells promotes liver injury and fibrosis in mice. Hepatology. 2006;44:1267–77.CrossRefPubMed Choi SS, Sicklick JK, Ma Q, et al. Sustained activation of Rac 1 in hepatic stellate cells promotes liver injury and fibrosis in mice. Hepatology. 2006;44:1267–77.CrossRefPubMed
32.
Zurück zum Zitat Staels B, Rubenstrunk A, Noel B, et al. Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology. 2013;58:1941–52.CrossRefPubMed Staels B, Rubenstrunk A, Noel B, et al. Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology. 2013;58:1941–52.CrossRefPubMed
33.
Zurück zum Zitat Puthawala K, Hadjiangelis N, Jacoby SC, et al. Inhibition of integrin alpha (v) beta6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis. Am J Respir Crit Care Med. 2008;177:82–90.CrossRefPubMed Puthawala K, Hadjiangelis N, Jacoby SC, et al. Inhibition of integrin alpha (v) beta6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis. Am J Respir Crit Care Med. 2008;177:82–90.CrossRefPubMed
34.
Zurück zum Zitat Henderson NC, Arnold TD, Katamura Y, et al. Targeting of alpha v integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013;19:1617–24.CrossRefPubMed Henderson NC, Arnold TD, Katamura Y, et al. Targeting of alpha v integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013;19:1617–24.CrossRefPubMed
35.
Zurück zum Zitat Sato Y, Murase K, Kato J, et al. Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat Biotechnol. 2008;26:431–42.CrossRefPubMed Sato Y, Murase K, Kato J, et al. Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat Biotechnol. 2008;26:431–42.CrossRefPubMed
36.
Zurück zum Zitat Barry-Hamilton V, Spangler R, Marshall D, et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med. 2010;16:1009–17.CrossRefPubMed Barry-Hamilton V, Spangler R, Marshall D, et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med. 2010;16:1009–17.CrossRefPubMed
37.
Zurück zum Zitat Gao B, Radaeva S, Park O. Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases. J Leukoc Biol. 2009;86:513–28.CrossRefPubMedPubMedCentral Gao B, Radaeva S, Park O. Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases. J Leukoc Biol. 2009;86:513–28.CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Chakraborty JB, Mann DA. NF-kB signalling: Embracing complexity to achieve translation. J Hepatol. 2010;52:285–91.CrossRefPubMed Chakraborty JB, Mann DA. NF-kB signalling: Embracing complexity to achieve translation. J Hepatol. 2010;52:285–91.CrossRefPubMed
39.
Zurück zum Zitat Forbes SJ, Rosenthal N. Preparing the ground for tissue regeneration: from mechanism to therapy. Nat Med. 2014;20:857–69.CrossRefPubMed Forbes SJ, Rosenthal N. Preparing the ground for tissue regeneration: from mechanism to therapy. Nat Med. 2014;20:857–69.CrossRefPubMed
40.
Zurück zum Zitat Than NN, Tomlinson CL, Haldar D, et al. Clinical effectiveness of cell therapies in patients with chronic liver disease and acute-on-chronic liver failure: a systematic review protocol. Syst Rev. 2016;5:100.CrossRefPubMedPubMedCentral Than NN, Tomlinson CL, Haldar D, et al. Clinical effectiveness of cell therapies in patients with chronic liver disease and acute-on-chronic liver failure: a systematic review protocol. Syst Rev. 2016;5:100.CrossRefPubMedPubMedCentral
41.
Zurück zum Zitat 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;24:2292–8.CrossRefPubMed 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;24:2292–8.CrossRefPubMed
42.
Zurück zum Zitat Terai S, Takami T, Yamamoto N, et al. Status and prospects of liver cirrhosis treatment by using bone marrow-derived cells and mesenchymal cells. Tissue Eng Part B Rev. 2014;20:206–10.CrossRefPubMed Terai S, Takami T, Yamamoto N, et al. Status and prospects of liver cirrhosis treatment by using bone marrow-derived cells and mesenchymal cells. Tissue Eng Part B Rev. 2014;20:206–10.CrossRefPubMed
43.
Zurück zum Zitat Kim JK, Park YN, Kim JS, et al. Autologous bone marrow infusion activates the progenitor cell compartment in patients with advanced liver cirrhosis. Cell Transplant. 2010;19:1237–46.CrossRefPubMed Kim JK, Park YN, Kim JS, et al. Autologous bone marrow infusion activates the progenitor cell compartment in patients with advanced liver cirrhosis. Cell Transplant. 2010;19:1237–46.CrossRefPubMed
44.
Zurück zum Zitat Saito T, Okumoto K, Haga H, et al. Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis. Stem Cells Dev. 2011;20:1503–10.CrossRefPubMed Saito T, Okumoto K, Haga H, et al. Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis. Stem Cells Dev. 2011;20:1503–10.CrossRefPubMed
45.
Zurück zum Zitat 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;24:1822–30.CrossRefPubMed 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;24:1822–30.CrossRefPubMed
46.
Zurück zum Zitat Levicar N, Pai M, Habib NA, et al. Long-term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+ cells in patients with chronic liver disease. Cell Prolif. 2008;41(Suppl 1):115–25.PubMed Levicar N, Pai M, Habib NA, et al. Long-term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+ cells in patients with chronic liver disease. Cell Prolif. 2008;41(Suppl 1):115–25.PubMed
47.
Zurück zum Zitat Khan AA, Parveen N, Mahaboob VS, et al. Safety and efficacy of autologous bone marrow stem cell transplantation through hepatic artery for the treatment of chronic liver failure: a preliminary study. Transplant Proc. 2008;40:1140–4.CrossRefPubMed Khan AA, Parveen N, Mahaboob VS, et al. Safety and efficacy of autologous bone marrow stem cell transplantation through hepatic artery for the treatment of chronic liver failure: a preliminary study. Transplant Proc. 2008;40:1140–4.CrossRefPubMed
48.
Zurück zum Zitat Pai M, Zacharoulis D, Milicevic MN, et al. Autologous infusion of expanded mobilized adult bone marrow-derived CD34+ cells into patients with alcoholic liver cirrhosis. Am J Gastroenterol. 2008;103:1952–8.CrossRefPubMed Pai M, Zacharoulis D, Milicevic MN, et al. Autologous infusion of expanded mobilized adult bone marrow-derived CD34+ cells into patients with alcoholic liver cirrhosis. Am J Gastroenterol. 2008;103:1952–8.CrossRefPubMed
49.
Zurück zum Zitat Han Y, Yan L, Han G, et al. Controlled trials in hepatitis B virus-related decompensate liver cirrhosis: peripheral blood monocyte transplant versus granulocyte-colony-stimulating factor mobilization therapy. Cytotherapy. 2008;10:390–6.CrossRefPubMed Han Y, Yan L, Han G, et al. Controlled trials in hepatitis B virus-related decompensate liver cirrhosis: peripheral blood monocyte transplant versus granulocyte-colony-stimulating factor mobilization therapy. Cytotherapy. 2008;10:390–6.CrossRefPubMed
50.
Zurück zum Zitat Spahr L, Lambert JF, Rubbia-Brandt L, et al. Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial. Hepatology. 2008;48:221–9.CrossRefPubMed Spahr L, Lambert JF, Rubbia-Brandt L, et al. Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial. Hepatology. 2008;48:221–9.CrossRefPubMed
51.
Zurück zum Zitat Salama H, Zekri AR, Bahnassy AA, et al. Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease. World J Gastroenterol. 2010;16:5297–305.CrossRefPubMedPubMedCentral Salama H, Zekri AR, Bahnassy AA, et al. Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease. World J Gastroenterol. 2010;16:5297–305.CrossRefPubMedPubMedCentral
52.
Zurück zum Zitat Salama H, Zekri AR, Zern M, et al. Autologous hematopoietic stem cell transplantation in 48 patients with end-stage chronic liver diseases. Cell Transplant. 2010;19:1475–86.CrossRefPubMed Salama H, Zekri AR, Zern M, et al. Autologous hematopoietic stem cell transplantation in 48 patients with end-stage chronic liver diseases. Cell Transplant. 2010;19:1475–86.CrossRefPubMed
53.
Zurück zum Zitat Garg V, Garg H, Khan A, et al. Granulocyte colony–stimulating factor mobilizes CD34+ cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology. 2012;142(505–512):e1. Garg V, Garg H, Khan A, et al. Granulocyte colony–stimulating factor mobilizes CD34+ cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology. 2012;142(505–512):e1.
54.
Zurück zum Zitat Kedarisetty CK, Anand L, Bhardwaj A, et al. Combination of granulocyte colony-stimulating factor and erythropoietin improves outcomes of patients with decompensated cirrhosis. Gastroenterology. 2015;148(1362–70):e7. Kedarisetty CK, Anand L, Bhardwaj A, et al. Combination of granulocyte colony-stimulating factor and erythropoietin improves outcomes of patients with decompensated cirrhosis. Gastroenterology. 2015;148(1362–70):e7.
55.
Zurück zum Zitat King A, Barton D, Beard HA, et al. REpeated AutoLogous Infusions of STem cells In Cirrhosis (REALISTIC): a multicentre, phase II, open-label, randomised controlled trial of repeated autologous infusions of granulocyte colony-stimulating factor (GCSF) mobilised CD133+ bone marrow stem cells in patients with cirrhosis. A study protocol for a randomised controlled trial. BMJ Open. 2015;5:e007700.CrossRefPubMedPubMedCentral King A, Barton D, Beard HA, et al. REpeated AutoLogous Infusions of STem cells In Cirrhosis (REALISTIC): a multicentre, phase II, open-label, randomised controlled trial of repeated autologous infusions of granulocyte colony-stimulating factor (GCSF) mobilised CD133+ bone marrow stem cells in patients with cirrhosis. A study protocol for a randomised controlled trial. BMJ Open. 2015;5:e007700.CrossRefPubMedPubMedCentral
56.
Zurück zum Zitat Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015;17:11–22.CrossRefPubMed Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015;17:11–22.CrossRefPubMed
57.
Zurück zum Zitat Banas A, Teratani T, Yamamoto Y, et al. Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology. 2007;46:219–28.CrossRefPubMed Banas A, Teratani T, Yamamoto Y, et al. Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology. 2007;46:219–28.CrossRefPubMed
58.
Zurück zum Zitat Seki A, Sakai Y, Komura T, et al. Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model. Hepatology. 2013;58:1133–42.CrossRefPubMed Seki A, Sakai Y, Komura T, et al. Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model. Hepatology. 2013;58:1133–42.CrossRefPubMed
59.
Zurück zum Zitat 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;1:725–31.CrossRefPubMedPubMedCentral 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;1:725–31.CrossRefPubMedPubMedCentral
60.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
61.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
62.
Zurück zum Zitat 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;23:2482–9.CrossRefPubMed 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;23:2482–9.CrossRefPubMed
64.
Zurück zum Zitat Lalu MM, McIntyre L, Pugliese C, et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7:e47559.CrossRefPubMedPubMedCentral Lalu MM, McIntyre L, Pugliese C, et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7:e47559.CrossRefPubMedPubMedCentral
65.
Zurück zum Zitat Omatsu Y, Seike M, Sugiyama T, et al. Foxc 1 is a critical regulator of haematopoietic stem/progenitor cell niche formation. Nature. 2014;508:536–40.CrossRefPubMed Omatsu Y, Seike M, Sugiyama T, et al. Foxc 1 is a critical regulator of haematopoietic stem/progenitor cell niche formation. Nature. 2014;508:536–40.CrossRefPubMed
66.
Zurück zum Zitat Wang Y, Chen X, Cao W, et al. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014;15:1009–16.CrossRefPubMed Wang Y, Chen X, Cao W, et al. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014;15:1009–16.CrossRefPubMed
67.
Zurück zum Zitat Katsuda T, Kosaka N, Takeshita F, et al. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. Proteomics. 2013;13:1637–53.CrossRefPubMed Katsuda T, Kosaka N, Takeshita F, et al. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. Proteomics. 2013;13:1637–53.CrossRefPubMed
68.
Zurück zum Zitat Monsel A, Zhu YG, Gudapati V, et al. Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases. Expert Opin Biol Ther. 2016;16:859–71.CrossRefPubMed Monsel A, Zhu YG, Gudapati V, et al. Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases. Expert Opin Biol Ther. 2016;16:859–71.CrossRefPubMed
69.
Zurück zum Zitat Park CM, Kim MJ, Kim SM, et al. Umbilical cord mesenchymal stem cell-conditioned media prevent muscle atrophy by suppressing muscle atrophy-related proteins and ROS generation. In Vitro Cell Dev Biol Anim. 2016;52:68–76.CrossRefPubMed Park CM, Kim MJ, Kim SM, et al. Umbilical cord mesenchymal stem cell-conditioned media prevent muscle atrophy by suppressing muscle atrophy-related proteins and ROS generation. In Vitro Cell Dev Biol Anim. 2016;52:68–76.CrossRefPubMed
70.
Zurück zum Zitat 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;13:3359–63.CrossRefPubMedPubMedCentral 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;13:3359–63.CrossRefPubMedPubMedCentral
71.
Zurück zum Zitat 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;10:459–66.PubMed 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;10:459–66.PubMed
72.
Zurück zum Zitat Kharaziha P, Hellstrom 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;21:1199–205.CrossRefPubMed Kharaziha P, Hellstrom 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;21:1199–205.CrossRefPubMed
73.
Zurück zum Zitat El-Ansary MMS, Abdel-Aziz I, Abdel-Hamid S. Phase I trial: mesenchymal stem cells transplantation in end stage liver disease. J Am Sci. 2010;6:135–44. El-Ansary MMS, Abdel-Aziz I, Abdel-Hamid S. Phase I trial: mesenchymal stem cells transplantation in end stage liver disease. J Am Sci. 2010;6:135–44.
74.
Zurück zum Zitat Amer ME, El-Sayed SZ, El-Kheir WA, et al. Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells. Eur J Gastroenterol Hepatol. 2011;23:936–41.CrossRefPubMed Amer ME, El-Sayed SZ, El-Kheir WA, et al. Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells. Eur J Gastroenterol Hepatol. 2011;23:936–41.CrossRefPubMed
75.
Zurück zum Zitat 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. Hepatology. 2011;54:820–8.CrossRefPubMed 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. Hepatology. 2011;54:820–8.CrossRefPubMed
76.
Zurück zum Zitat 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. 2012;8:972–81.CrossRefPubMed 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. 2012;8:972–81.CrossRefPubMed
77.
Zurück zum Zitat Mohamadnejad M, Alimoghaddam K, Bagheri M, et al. Randomized placebo-controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis. Liver Int. 2013;33:1490–6.PubMed Mohamadnejad M, Alimoghaddam K, Bagheri M, et al. Randomized placebo-controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis. Liver Int. 2013;33:1490–6.PubMed
78.
Zurück zum Zitat Amin MA, Sabry D, Rashed LA, et al. Short-term evaluation of autologous transplantation of bone marrow-derived mesenchymal stem cells in patients with cirrhosis: Egyptian study. Clin Transplant. 2013;27:607–12.CrossRefPubMed Amin MA, Sabry D, Rashed LA, et al. Short-term evaluation of autologous transplantation of bone marrow-derived mesenchymal stem cells in patients with cirrhosis: Egyptian study. Clin Transplant. 2013;27:607–12.CrossRefPubMed
79.
Zurück zum Zitat 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;34:33–41.CrossRefPubMed 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;34:33–41.CrossRefPubMed
80.
Zurück zum Zitat Salama H, Zekri AR, Medhat E, et al. Peripheral vein infusion of autologous mesenchymal stem cells in Egyptian HCV-positive patients with end-stage liver disease. Stem Cell Res Ther. 2014;5:70.CrossRefPubMedPubMedCentral Salama H, Zekri AR, Medhat E, et al. Peripheral vein infusion of autologous mesenchymal stem cells in Egyptian HCV-positive patients with end-stage liver disease. Stem Cell Res Ther. 2014;5:70.CrossRefPubMedPubMedCentral
81.
Zurück zum Zitat 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;29:1620–8.CrossRefPubMed 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;29:1620–8.CrossRefPubMed
82.
Zurück zum Zitat Lukashyk SP, Tsyrkunov VM, Isaykina YI, et al. Mesenchymal bone marrow-derived stem cells transplantation in patients with HCV related liver cirrhosis. J Clin Transl Hepatol. 2014;2:217–21.PubMedPubMedCentral Lukashyk SP, Tsyrkunov VM, Isaykina YI, et al. Mesenchymal bone marrow-derived stem cells transplantation in patients with HCV related liver cirrhosis. J Clin Transl Hepatol. 2014;2:217–21.PubMedPubMedCentral
83.
Zurück zum Zitat 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. doi:10.1002/hep.28693.PubMed 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. doi:10.​1002/​hep.​28693.PubMed
84.
Zurück zum Zitat 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;29:898–909.CrossRefPubMed 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;29:898–909.CrossRefPubMed
85.
Zurück zum Zitat Chang YJ, Liu JW, Lin PC, et al. Mesenchymal stem cells facilitate recovery from chemically induced liver damage and decrease liver fibrosis. Life Sci. 2009;85:517–25.CrossRefPubMed Chang YJ, Liu JW, Lin PC, et al. Mesenchymal stem cells facilitate recovery from chemically induced liver damage and decrease liver fibrosis. Life Sci. 2009;85:517–25.CrossRefPubMed
86.
Zurück zum Zitat Kim SJ, Park KC, Lee JU, et al. Therapeutic potential of adipose tissue-derived stem cells for liver failure according to the transplantation routes. J Korean Surg Soc. 2011;81:176–86.CrossRefPubMedPubMedCentral Kim SJ, Park KC, Lee JU, et al. Therapeutic potential of adipose tissue-derived stem cells for liver failure according to the transplantation routes. J Korean Surg Soc. 2011;81:176–86.CrossRefPubMedPubMedCentral
87.
Zurück zum Zitat Tanimoto H, Terai S, Taro T, et al. Improvement of liver fibrosis by infusion of cultured cells derived from human bone marrow. Cell Tissue Res. 2013;354:717–28.CrossRefPubMed Tanimoto H, Terai S, Taro T, et al. Improvement of liver fibrosis by infusion of cultured cells derived from human bone marrow. Cell Tissue Res. 2013;354:717–28.CrossRefPubMed
88.
Zurück zum Zitat Jang YO, Kim MY, Cho MY, et al. Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model. BMC Gastroenterol. 2014;14:198.CrossRefPubMedPubMedCentral Jang YO, Kim MY, Cho MY, et al. Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model. BMC Gastroenterol. 2014;14:198.CrossRefPubMedPubMedCentral
89.
90.
Zurück zum Zitat Duffield JS, Forbes SJ, Constandinou CM, et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest. 2005;115:56–65.CrossRefPubMedPubMedCentral Duffield JS, Forbes SJ, Constandinou CM, et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest. 2005;115:56–65.CrossRefPubMedPubMedCentral
91.
Zurück zum Zitat Ramachandran P, Pellicoro A, Vernon MA, et al. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc Natl Acad Sci U S A. 2012;109:E3186–95.CrossRefPubMedPubMedCentral Ramachandran P, Pellicoro A, Vernon MA, et al. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc Natl Acad Sci U S A. 2012;109:E3186–95.CrossRefPubMedPubMedCentral
92.
Zurück zum Zitat Bird TG, Lu WY, Boulter L, et al. Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling. Proc Natl Acad Sci U S A. 2013;110:6542–7.CrossRefPubMedPubMedCentral Bird TG, Lu WY, Boulter L, et al. Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling. Proc Natl Acad Sci U S A. 2013;110:6542–7.CrossRefPubMedPubMedCentral
93.
Zurück zum Zitat Boulter L, Govaere O, Bird TG, et al. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nat Med. 2012;18:572–9.CrossRefPubMedPubMedCentral Boulter L, Govaere O, Bird TG, et al. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nat Med. 2012;18:572–9.CrossRefPubMedPubMedCentral
94.
95.
Zurück zum Zitat Moore JK, Mackinnon AC, Wojtacha D, et al. Phenotypic and functional characterization of macrophages with therapeutic potential generated from human cirrhotic monocytes in a cohort study. Cytotherapy. 2015;17:1604–16.CrossRefPubMedPubMedCentral Moore JK, Mackinnon AC, Wojtacha D, et al. Phenotypic and functional characterization of macrophages with therapeutic potential generated from human cirrhotic monocytes in a cohort study. Cytotherapy. 2015;17:1604–16.CrossRefPubMedPubMedCentral
Metadaten
Titel
Status of and candidates for cell therapy in liver cirrhosis: overcoming the “point of no return” in advanced liver cirrhosis
verfasst von
Shuji Terai
Atsunori Tsuchiya
Publikationsdatum
08.09.2016
Verlag
Springer Japan
Erschienen in
Journal of Gastroenterology / Ausgabe 2/2017
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-016-1258-1

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