Clinical Application of Stem Cell Therapy for Liver Cirrhosis: Progress, Pitfalls, and Prospects
Keywords:
stem cells, liver cirrhosis, regenerative medicineAbstract
Liver cirrhosis is the advanced stage of liver disease accounting for high morbidity and mortality rates worldwide. Liver transplantation for liver cirrhosis has several limitations, rendering stem cell transplantation as a potential therapy. Clinical trials of stem cell applications for liver cirrhosis are being established using various types of stem cells. This review will provide a current report of the achievements, limitations, and future directions of stem cell transplantation. Current progress of clinical trials is valuable in defining the best type of stem cells, mode of delivery, the number and frequency of cells to be injected, and determining potential candidates for cell therapy. Some of the encountered pitfalls are the limited homing and differentiation potential of stem cells, the use of non-xenofree culture system, and the risk for tumorigenesis in certain types of stem cells. The prospective developments of liver stem cell transplantation are the generation of genetically modified stem cells and the formation of liver organoids for treating liver cirrhosis.References
Zhang Y, Li Y, Zhang L, et al. Mesenchymal stem cells: potential application for the treatment of hepatic cirrhosis. Stem Cell Res Ther. 2018;9(1):59.
Berardis S, Sattwika PD, Najimi M, Sokal EM. Use of mesenchymal stem cells to treat liver fibrosis: current situation and future prospects. World J Gastroenterol. 2015;21(3):742–758.
Forbes SJ, Gupta S, Dhawan A. Cell therapy for liver disease: from liver transplantation to cell factory. J Hepatol. 2015;62(S1):S157–S169.
Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology. 2010;134(6):1655–69.
Mohamadnejad M, Alimoghaddam K, Bagheri M, et al. Randomized placebo-controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis. Liver Int. 2013;33(10):1490–6.
Lyra AC, Soares MB, da Silva LF, et al. Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease. World J Gastroenterol. 2007;13(7):1067–73.
Gordon MY, Levičar 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):1822–30.
Amer M-EM, 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(10):936–41.
El-ansary M, Abdel-aziz I. Phase II trial: undifferentiated versus differentiated autologous mesenchymal stem cells transplantation in egyptian patients with HCV induced liver cirrhosis. Stem Cell Rev Rep. 2012;8:972–81.
Gaia S, Smedile A, Omedè P, et al. Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease. J Hepatol. 2006;45(1):13–9.
Kwak K-A, Lee S-P, Yang J-Y, Park Y-S. Current perspectives regarding stem cell-based therapy for liver cirrhosis. Can J Gastroenterol Hepatol. 2018;2018:1–14.
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.
Cohen-Naftaly M, Friedman SL. Current status of novel antifibrotic therapies in patients with chronic liver disease. Therap Adv Gastroenterol. 2011;4(6):391–417.
Lin H, Xu R, Zhang Z, et al. Implications of the immunoregulatory functions of mesenchymal stem cells in the treatment of human liver diseases. Cell Mol Immunol. 2011;8(1):19–22.
Eom YW, Shim KY, Baik SK. Mesenchymal stem cell therapy for liver fibrosis. Korean J Intern Med. 2015;(2):510–6.
Nicolas C, Wang Y, Luebke-Wheeler J, Nyberg S. Stem cell therapies for treatment of liver disease. Biomedicines. 2016;4(1):2.
am Esch JS, Knoefel WT, Klein M, et al. Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration. Stem Cells. 2005;23(4):463–70.
Bahk JY, Piao Z, Jung JH, Han H. Treatment of the end stage liver cirrhosis by human umbilical cord blood stem cells: preliminary results. In: Stem Cells in Clinic and Research, Dr Ali Gholamrezanezhad (Ed). InTech. 2011. p. 469–500.
Gholamrezanezhad A, Mirpour S, Bagheri M, Mohamadnejad M. In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis. Nucl Med Biol. 2011;38(7):961–7.
Suk KT, Yoon J-H, 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.
Zhao L, Chen S, Shi X, Cao H. A pooled analysis of mesenchymal stem cell-based therapy for liver disease. Stem Cell Res Ther. 2018;9:1–13.
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. Cell Prolif. 2008;41(1):115–25.
Peng L, Xie D, Lin B, 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;820–8.
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):3359–63.
Newsome PN, Fox R, King AL, et al. Granulocyte colony-stimulating factor and autologous CD133-positive stem-cell therapy in liver cirrhosis (REALISTIC): an open-label, randomised, controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2017;1253(17):4–6.
Liu WH, Song FQ, Ren LN, et al. The multiple functional roles of mesenchymal stem cells in participating in treating liver diseases. J Cell Mol Med. 2015;19(3):511–20.
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(10):1237–46.
Shahjalal HM, Shiraki N, Sakano D, et al. Generation of insulin-producing beta-like cells from human iPS cells in a defined and completely xeno-free culture system. J Mol Cell Biol. 2014;6(5):394–408.
Mitsui K, Ide K, Takahashi T, Kosai KI. Viral vector-based innovative approaches to directly abolishing tumorigenic pluripotent stem cells for safer regenerative medicine. Mol Ther Methods Clin Dev. 2017;5(June):51–8.
Phillips MI, Tang YL. Genetic modification of stem cells for transplantation. Adv Drug Deliv Rev. 2008;60(2):160–72.
Huch M, Koo B-K. Modeling mouse and human development using organoid cultures. Development. 2015;142(18):3113–3125.
Takebe T, Sekine K, Kimura M, et al. Massive and reproducible production of liver buds entirely from human pluripotent stem cells. Cell Rep. 2017;21(10):2661–70.
Downloads
Published
How to Cite
Issue
Section
License
Copyright
The authors who publish in this journal agree to the following requirements:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors can enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) before and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. (See The Effect of Open Access)
Privacy Statement
The names and email addresses entered in this journal site will be used exclusively for the stated purposes of this journal and will not be made available for any other purpose or to any other party.
