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Current Stem Cell Research & Therapy

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ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

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Meta-Analysis

Mesenchymal Stem Cell Therapy for Acetaminophen-related Liver Injury: A Systematic Review and Meta-analysis of Experimental Studies In Vivo

Author(s): Li Wang, Yiwen Zhang , Jiajun Zhong, Yuan Zhang, Shuisheng Zhou* and Chengfang Xu *

Volume 17, Issue 8, 2022

Published on: 26 November, 2021

Page: [825 - 838] Pages: 14

DOI: 10.2174/1574888X16666211007092055

Price: $65

Abstract

Objective: The efficacy of mesenchymal stem cell (MSC) therapy in acetaminophen-induced liver injury has been investigated in animal experiments, but individual studies with a small sample size cannot be used to draw a clear conclusion. Therefore, we conducted a systematic review and meta-analysis of preclinical studies to explore the potential of using MSCs in acetaminophen- induced liver injury.

Methods: Eight databases were searched for studies reporting the effects of MSCs on acetaminophen hepatoxicity. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. SYRCLE’s risk of bias tool for animal studies was applied to assess the methodological quality. A meta-analysis was performed by using RevMan 5.4 and STATA/ SE 16.0 software.

Results: Eleven studies involving 159 animals were included according to PRISMA statement guidelines. Significant associations were found for MSCs with the levels of alanine transaminase (ALT) (standardized mean difference (SMD) - 2.58, p < 0.0001), aspartate aminotransferase (AST) (SMD - 1.75, p = 0.001), glutathione (GSH) (SMD 3.7, p < 0.0001), superoxide dismutase (SOD) (SMD 1.86, p = 0.022), interleukin 10 (IL-10) (SMD 5.14, p = 0.0002) and tumor necrosis factor-α (TNF-α) (SMD - 4.48, p = 0.011) compared with those in the control group. The subgroup analysis showed that the tissue source of MSCs significantly affected the therapeutic efficacy (p < 0.05).

Conclusion: Our meta-analysis results demonstrate that MSCs could be a potential treatment for acetaminophen- related liver injury. The protocol for this meta-analysis was prospectively registered in PROSPERO (Number: CRD42020212677).

Keywords: Acetaminophen, drug-induced liver injury, mesenchymal stem cell, therapeutic efficacy, systematic review, meta-analysis.

« Previous Next »
[1]
Jaeschke H. Acetaminophen: dose-dependent drug hepatotoxicity and acute liver failure in patients. Dig Dis 2015; 33(4): 464-71.
[2]
Bernal W, Wendon J. Acute liver failure. N Engl J Med 2013; 369(26): 2525-34.
[3]
Koch DG, Speiser JL, Durkalski V, et al. The natural history of severe acute liver injury. Am J Gastroenterol 2017; 112(9): 1389-96.
[4]
Bernal W, Lee WM, Wendon J, Larsen FS, Williams R. Acute liver failure: A curable disease by 2024? J Hepatol 2015; 62(1 Suppl): S112-20.
[5]
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]
[6]
Lancaster EM, Hiatt JR, Zarrinpar A. Acetaminophen hepatotoxicity: An updated review. Arch toxicol 2015; 89(2): 193-9.
[http://dx.doi.org/10.1007/s00204-014-1432-2]
[7]
Jaeschke H, Williams CD, Ramachandran A, Bajt ML. Acetaminophen hepatotoxicity and repair: The role of sterile inflammation and innate immunity. Liver int 2012; 32(1): 8-20.
[http://dx.doi.org/10.1111/j.1478-3231.2011.02501.x]
[8]
Bunchorntavakul C, Reddy KR. Acetaminophen-related hepatotoxicity. Clin liver dis 2013; 17(4): 587-607.
[http://dx.doi.org/10.1016/j.cld.2013.07.005]
[9]
Lee WM. Acetaminophen (APAP) hepatotoxicity-Isn't it time for APAP to go away? J Hepatol 2017; 67(6): 1324-31.
[10]
Craig DG, Lee A, Hayes PC, Simpson KJ. Review article: the current management of acute liver failure. Aliment Pharmacol Ther 2010; 31(3): 345-58.
[http://dx.doi.org/10.1111/j.1365-2036.2009.04175.x]
[11]
Hu C, Zhao L, Wu Z, Li L. Transplantation of mesenchymal stem cells and their derivatives effectively promotes liver regeneration to attenuate acetaminophen-induced liver injury. Stem cell res ther 2020; 11(1): 88.
[http://dx.doi.org/10.1186/s13287-020-01596-9]
[12]
Germani G, Theocharidou E, Adam R, et al. Liver transplantation for acute liver failure in Europe: Outcomes over 20 years from the ELTR database. J Hepatol 2012; 57(2): 288-96.
[13]
Alfaifi M, Eom YW, Newsome PN, Baik SK. Mesenchymal stromal cell therapy for liver diseases. J Hepatol 2018; 68(6): 1272-85.
[14]
Kholodenko IV, Kurbatov LK, Kholodenko RV, Manukyan GV, Yarygin KN. Mesenchymal stem cells in the adult human liver: hype or hope? Cells-Basel 2019; 8(10).
[15]
Kouroupis D, Sanjurjo-Rodriguez C, Jones E, Correa D. Mesenchymal stem cell functionalization for enhanced therapeutic applications. Tissue Eng Part B Rev 2019; 25(1): 55-77.
[http://dx.doi.org/10.1089/ten.teb.2018.0118]
[16]
Dolati S, Yousefi M, Mahdipour M, et al. Mesenchymal stem cell and bone marrow mononuclear cell therapy for cardiomyopathy: From bench to bedside. J Cell Biochem 2019; 120(1): 45-55.
[17]
Zhang H, Li ZL, Yang F, et al. Radial shockwave treatment promotes human mesenchymal stem cell self-renewal and enhances cartilage healing. Stem Cell Res Ther 2018; 9(1): 54.
[http://dx.doi.org/10.1186/s13287-018-0805-5]
[18]
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.
[19]
El AE, Kramann R, Schneider RK, et al. Mesenchymal stem cells in fibrotic disease. Cell Stem Cell 2017; 21(2): 166-77.
[20]
Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell stem cell 2015; 17(1): 11-22.
[21]
Forbes SJ, Gupta S, Dhawan A. Cell therapy for liver disease: From liver transplantation to cell factory. J Hepatol 2015; 62(1 Suppl): S157-69.
[22]
Higgins JPT, Thomas J, Chandler J, et al. Cochrane handbook for systematic reviews of interventions. 2nd Ed. Chichester, UK: John Wiley & Sons 2019.
[http://dx.doi.org/10.1002/9781119536604]
[23]
Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4: 1.
[24]
Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE's risk of bias tool for animal studies. BMC Med Res Methodol 2014; 14: 43.
[25]
Wassenaar P, Trasande L, Legler J. Systematic review and meta-analysis of early-life exposure to bisphenol A and obesity-related outcomes in rodents. Environ Health Perspect 2017; 125(10): 106001.
[http://dx.doi.org/10.1289/EHP1233]
[26]
Shi X, Chen Q, Wang F. Mesenchymal stem cells for the treatment of ulcerative colitis: a systematic review and meta-analysis of experimental and clinical studies. Stem Cell Res Ther 2019; 10(1): 266.
[http://dx.doi.org/10.1186/s13287-019-1336-4]
[27]
Zou ZY, Zhou ZR, Che CH, Liu CY, He RL, Huang HP. Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2017; 88(7): 540-9.
[28]
Tang Y, Li Q, Meng F, et al. Therapeutic potential of HGF-expressing human umbilical cord mesenchymal stem cells in mice with acute liver failure. Int J Hepatol 2016; 2016: 5452487.
[29]
Hwang Y, Kim JC, Tae G. Significantly enhanced recovery of acute liver failure by liver targeted delivery of stem cells via heparin functionalization. Biomaterials 2019; 209: 67-78.
[http://dx.doi.org/10.1016/j.biomaterials.2019.04.019]
[30]
Huang YJ, Chen P, Lee CY, et al. Protection against acetaminophen-induced acute liver failure by omentum adipose tissue derived stem cells through the mediation of Nrf2 and cytochrome P450 expression. J Biomed Sci 2016; 23: 5.
[31]
Chetty SS, Praneetha S, Govarthanan K, Verma RS, Vadivel MA. Noninvasive tracking and regenerative capabilities of transplanted human umbilical cord-derived mesenchymal stem cells labeled with i-iii-iv semiconducting nanocrystals in liver-injured living mice. ACS Appl Mater Interfaces 2019; 11(9): 8763-78.
[http://dx.doi.org/10.1021/acsami.8b19953]
[32]
Liu Z, Meng F, Li C, et al. Human umbilical cord mesenchymal stromal cells rescue mice from acetaminophen-induced acute liver failure. Cytotherapy 2014; 16(9): 1207-19.
[http://dx.doi.org/10.1016/j.jcyt.2014.05.018]
[33]
Hua D, Ju Z, Gan X, et al. Human amniotic mesenchymal stromal cells alleviate acute liver injury by inhibiting the pro-inflammatory response of liver resident macrophage through autophagy. Ann Transl Med 2019; 7(16): 392.
[http://dx.doi.org/10.21037/atm.2019.08.83]
[34]
Salomone F, Barbagallo I, Puzzo L, Piazza C, Li VG. Efficacy of adipose tissue-mesenchymal stem cell transplantation in rats with acetaminophen liver injury. Stem Cell Res 2013; 11(3): 1037-44.
[35]
Mullick M, Banerjee S, Sen D. Amelioration of acetaminophen-induced liver injury via delta opioid receptor-activated human mesenchymal stem cells-an in vivo approach. Regen Eng Transl Med 2019; 5(3): 263-9.
[http://dx.doi.org/10.1007/s40883-019-00101-w]
[36]
Liu YD, Yang YS, Wang YF, et al. Experimental study of transplanting human mesenchymal stem cells via portal vein to treat acute liver injury of mice induced with acetaminophen. Zhonghua Gan Zang Bing Za Zhi 2008; 16(9): 688-91.
[37]
Ying-Di L, Yun-Sheng Y, Yun-Fang W, et al. Curative effect of transsplenic human mesochymal stem cells transplantation on acetaminophen-induced acute liver injury in mice. World Chinese Journal of Digestology 2008; 18: 1969-73.
[38]
Liu YD. Experimental study of human mesochymal stem cells transplantation to the mouse of acetaminophen induced acute liver injury. PLA Military Medical Refresher College 2007.
[39]
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.
[40]
Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: An update. Cell Transplant 2016; 25(5): 829-48.
[41]
Ding DC, Chang YH, Shyu WC, Lin SZ. Human umbilical cord mesenchymal stem cells: A new era for stem cell therapy. Cell Transplant 2015; 24(3): 339-47.
[http://dx.doi.org/10.3727/096368915X686841]
[42]
Hu C, Zhao L, Li L. Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases. Stem Cell Res Ther 2019; 10(1): 199.
[http://dx.doi.org/10.1186/s13287-019-1310-1]
[43]
Choudhery MS, Badowski M, Muise A, Harris DT. Comparison of human mesenchymal stem cells derived from adipose and cord tissue. Cytotherapy 2013; 15(3): 330-43.
[http://dx.doi.org/10.1016/j.jcyt.2012.11.010]
[44]
Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006; 24(5): 1294-301.
[http://dx.doi.org/10.1634/stemcells.2005-0342]
[45]
Jin HJ, Bae YK, Kim M, et al. Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int J Mol Sci 2013; 14(9): 17986-8001.
[http://dx.doi.org/10.3390/ijms140917986]
[46]
Mohamed-Ahmed S, Fristad I, Lie SA, et al. Adipose-derived and bone marrow mesenchymal stem cells: A donor-matched comparison. Stem Cell Res Ther 2018; 9(1): 168.
[http://dx.doi.org/10.1186/s13287-018-0914-1]
[47]
Sakai Y, Takamura M, Seki A, et al. Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell. Regen Ther 2017; 6: 52-64.
[48]
Li T, Xia M, Gao Y, Chen Y, Xu Y. Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy. Expert Opin Biol Ther 2015; 15(9): 1293-306.
[http://dx.doi.org/10.1517/14712598.2015.1051528]
[49]
Spriet M, Hunt GB, Walker NJ, Borjesson DL. Scintigraphic tracking of mesenchymal stem cells after portal, systemic intravenous and splenic administration in healthy beagle dogs. Vet Radiol Ultrasound 2015; 56(3): 327-34.
[http://dx.doi.org/10.1111/vru.12243]
[50]
Yukawa H, Watanabe M, Kaji N, et al. Monitoring transplanted adipose tissue-derived stem cells combined with heparin in the liver by fluorescence imaging using quantum dots. Biomaterials 2012; 33(7): 2177-86.
[http://dx.doi.org/10.1016/j.biomaterials.2011.12.009]
[51]
Li Z, Hu X, Mao J, et al. Optimization of mesenchymal stem cells (MSCs) delivery dose and route in mice with acute liver injury by bioluminescence imaging. Mol Imaging Biol 2015; 17(2): 185-94.
[52]
Deng L, Kong X, Liu G, et al. Transplantation of adipose-derived mesenchymal stem cells efficiently rescues thioacetamide-induced acute liver failure in mice. Transplant Proc 2016; 48(6): 2208-15.
[http://dx.doi.org/10.1016/j.transproceed.2016.02.077]
[53]
Zhao L, Chen S, Shi X, Cao H, Li L. A pooled analysis of mesenchymal stem cell-based therapy for liver disease. Stem Cell Res Ther 2018; 9(1): 72.
[http://dx.doi.org/10.1186/s13287-018-0816-2]
[54]
Tsuchiya A, Takeuchi S, Watanabe T, et al. Mesenchymal stem cell therapies for liver cirrhosis: MSCs as "conducting cells" for improvement of liver fibrosis and regeneration. Inflamm Regen 2019; 39(18)
[55]
Ghanem CI, Perez MJ, Manautou JE, Mottino AD. Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity. PHARMACOL RES 2016; 109: 119-31.
[56]
Ramachandran A, Lebofsky M, Weinman SA, Jaeschke H. The impact of partial manganese superoxide dismutase (SOD2)-deficiency on mitochondrial oxidant stress, DNA fragmentation and liver injury during acetaminophen hepatotoxicity. Toxicol Appl Pharmacol 2011; 251(3): 226-33.
[57]
Fujimoto K, Kumagai K, Ito K, et al. Sensitivity of liver injury in heterozygous Sod2 knockout mice treated with troglitazone or acetaminophen. Toxicol Pathol 2009; 37(2): 193-200.
[http://dx.doi.org/10.1177/0192623308329282]
[58]
Bourdi M, Masubuchi Y, Reilly TP, et al. Protection against acetaminophen-induced liver injury and lethality by interleukin 10: role of inducible nitric oxide synthase. Hepatology 2002; 35(2): 289-98.
[59]
Gandhi A, Guo T, Ghose R. Role of c-Jun N-terminal kinase (JNK) in regulating tumor necrosis factor-alpha (TNF-alpha) mediated increase of acetaminophen (APAP) and chlorpromazine (CPZ) toxicity in murine hepatocytes. J TOXICOL SCI 2010; 35(2): 163-73.
[60]
Tan CY, Lai RC, Wong W, Dan YY, Lim SK, Ho HK. Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. STEM CELL RES THER 2014; 5(3): 76.
[http://dx.doi.org/10.1186/scrt465]
[61]
Temnov A, Rogov K, Zhalimov V, et al. The effect of a mesenchymal stem cell conditioned medium fraction on morphological characteristics of hepatocytes in acetaminophen-induced acute liver failure: a preliminary study. Hepat Med 2019; 11: 89-96.
[http://dx.doi.org/10.2147/HMER.S196354]
[62]
Khubutiya M, Temnov AA, Vagabov VA, Sklifas AN, Rogov KA, Zhgutov YA. Effect of conditioned medium and bone marrow stem cell lysate on the course of acetaminophen-induced liver failure. Bull Exp Biol Med 2015; 159(1): 118-23.
[http://dx.doi.org/10.1007/s10517-015-2905-x]

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