본문 바로가기
KERD
논문KCI 등재

Mesenchymal Stem Cell Therapy in Acute Liver Failure

Wang Yong-Hong|Chen En-Qiang
거트앤리버 소화기연관학회협의회|2023.09|Gut and Liver|제17권 제5호|pp. 674-683|DOI 10.5009/gnl220417

1

조회

0

다운로드

1

인용

0

참고문헌

키워드

ImmunomodulationMesenchymal stem cellsAcute liver failureHepatocyte-like cells

초록

Acute liver failure (ALF) is a severe liver disease syndrome with rapid deterioration and high mortality. Liver transplantation is the most effective treatment, but the lack of donor livers and the high cost of transplantation limit its broad application. In recent years, there has been no breakthrough in the treatment of ALF, and the application of stem cells in the treatment of ALF is a crucial research field. Mesenchymal stem cells (MSCs) are widely used in disease treatment research due to their abundant sources, low immunogenicity, and no ethical restrictions. Although MSCs are effective for treating ALF, the application of MSCs to ALF needs to be further studied and optimized. In this review, we discuss the potential mechanisms of MSCs therapy for ALF, summarize some methods to enhance the efficacy of MSCs, and explore optimal approaches for MSC transplantation.

Abstract

Acute liver failure (ALF) is a severe liver disease syndrome with rapid deterioration and high mortality. Liver transplantation is the most effective treatment, but the lack of donor livers and the high cost of transplantation limit its broad application. In recent years, there has been no breakthrough in the treatment of ALF, and the application of stem cells in the treatment of ALF is a crucial research field. Mesenchymal stem cells (MSCs) are widely used in disease treatment research due to their abundant sources, low immunogenicity, and no ethical restrictions. Although MSCs are effective for treating ALF, the application of MSCs to ALF needs to be further studied and optimized. In this review, we discuss the potential mechanisms of MSCs therapy for ALF, summarize some methods to enhance the efficacy of MSCs, and explore optimal approaches for MSC transplantation.

참고문헌 (94)

  1. Saliba F, "Acute liver failure : current trends", J Hepatol, 59, pp.6~8 (2013)
  2. Olivo R, "Liver transplantation for acute liver failure", Clin Liver Dis, 22, pp.409~417 (2018)
  3. Tandon R, "Artificial liver support systems", J Gastroenterol Hepatol, 36, pp.1164~1179 (2021)
  4. Kelly K, "Mesenchymal stromal cells for the treatment of graft versus host disease", Front Immunol, 12, pp.761616~ (2021)
  5. Guohua Lou, "Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases", Experimental and Molecular Medicine, 49, pp.1~9 (2017), 생화학분자생물학회
  6. Qi Y, "Applicability of adipose-derived mesenchymal stem cells in treatment of patients with type 2diabetes", Stem Cell Res Ther, 10, pp.274~ (2019)
  7. Fu X, "Mesenchymal stem cell migration and tissue repair", Cells, 8, pp.784~ (2019)
  8. Shang L, "Immunomodulatory functions of oral mesenchymal stem cells : novel force for tissue regeneration and disease therapy", J Leukoc Biol, 110, pp.539~552 (2021)
  9. Ankrum JA, "Mesenchymal stem cells : immune evasive, not immune privileged", Nat Biotechnol, 32, pp.252~260 (2014)
  10. Hu C, "In vitro culture of isolated primary hepatocytes and stem cell-derived hepatocyte-like cells for liver regeneration", Protein Cell, 6, pp.562~574 (2015)
  11. Hu C, "Mesenchymal stem cellbased cell-free strategies : safe and effective treatments for liver injury", Stem Cell Res Ther, 11, pp.377~ (2020)
  12. Volarevic V, "Concise review : therapeutic potential of mesenchymal stem cells for the treatment of acute liver failure and cirrhosis", Stem Cells, 32, pp.2818~2823 (2014)
  13. Lee KD, "In vitro hepatic differentiation of human mesenchymal stem cells", Hepatology, 40, pp.1275~1284 (2004)
  14. Manzini BM, "Useful properties of undifferentiated mesenchymal stromal cells and adipose tissue as the source in liver-regenerative therapy studied in an animal model of severe acute fulminant hepatitis", Cytotherapy, 17, pp.1052~1065 (2015)
  15. Xin J, "Human bone marrow mesenchymal stem cell-derived hepatocytes express tissue inhibitor of metalloproteinases 4 and follistatin", Liver Int, 35, pp.2301~2310 (2015)
  16. Banas A, "Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure", J Gastroenterol Hepatol, 24, pp.70~77 (2009)
  17. Choi J, "Efficient hepatic differentiation and regeneration potential under xeno-free conditions using mass-producible amnion-derived mesenchymal stem cells", Stem Cell Res Ther, 12, pp.569~ (2021)
  18. Luo X, "Directed differentiation of adult liver derived mesenchymal like stem cells into functional hepatocytes", Sci Rep, 8, pp.2818~ (2018)
  19. Tao XR, "Clonal mesenchymal stem cells derived from human bone marrow can differentiate into hepatocyte-like cells in injured livers of SCID mice", J Cell Biochem, 108, pp.693~704 (2009)
  20. Chen G, "Adipose-derived stem cellbased treatment for acute liver failure", Stem Cell Res Ther, 6, pp.40~ (2015)
  21. Xiao JQ, "Administration of IL-1Ra chitosan nanoparticles enhances the therapeutic efficacy of mesenchymal stem cell transplantation in acute liver failure", Arch Med Res, 44, pp.370~379 (2013)
  22. Yang JF, "Mesenchymal stem cells from the human umbilical cord ameliorate fulminant hepatic failure and increase survival in mice", Hepatobiliary Pancreat Dis Int, 14, pp.186~193 (2015)
  23. Yu J, "In vivo hepatic differentiation of mesenchymal stem cells from human umbilical cord blood after transplantation into mice with liver injury", Biochem Biophys Res Commun, 422, pp.539~545 (2012)
  24. Wang H, "How important is differentiation in the therapeutic effect of mesenchymal stromal cells in liver disease?", Cytotherapy, 16, pp.309~318 (2014)
  25. Zagoura DS, "Therapeutic potential of a distinct population of human amniotic fluid mesenchymal stem cells and their secreted molecules in mice with acute hepatic failure", Gut, 61, pp.894~906 (2012)
  26. Zhou R, "Human umbilical cord mesenchymal stem cells and derived hepatocyte-like cells exhibit similar therapeutic effects on an acute liver failure mouse model", PLoS One, 9, pp.e104392~ (2014)
  27. Li D, "Therapeutic effect comparison of hepatocyte-like cells and bone marrow mesenchymal stem cells in acute liver failure of rats", Int J Clin Exp Pathol, 8, pp.11~24 (2015)
  28. Maheshwari D, "Bioenergetic failure drives functional exhaustion of monocytes in acute-onchronic liver failure", Front Immunol, 13, pp.856587~ (2022)
  29. Guo G, "Peripheral infusion of human umbilical cord mesenchymal stem cells rescues acute liver failure lethality in monkeys", Stem Cell Res Ther, 10, pp.84~ (2019)
  30. Gazdic M, "Crosstalk between mesenchymal stem cells and T regulatory cells is crucially important for the attenuation of acute liver injury", Liver Transpl, 24, pp.687~702 (2018)
  31. Zhang Y, "Mesenchymal stem cells alleviate bacteria-induced liver injury in mice by inducing regulatory dendritic cells", Hepatology, 59, pp.671~682 (2014)
  32. Li Y, "STAT6 up-regulation amplifies M2 macrophage anti-inflammatory capacity through mesenchymal stem cells", Int Immunopharmacol, 91, pp.107266~ (2021)
  33. Li YW, "Mesenchymal stem cells rescue acute hepatic failure by polarizing M2 macrophages", World J Gastroenterol, 23, pp.7978~7988 (2017)
  34. Wang J, "Mesenchymal stem cell-secreted prostaglandin E2 ameliorates acute liver failure via attenuation of cell death and regulation of macrophage polarization", Stem Cell Res Ther, 12, pp.15~ (2021)
  35. Akiyama K, "Mesenchymal-stemcell-induced immunoregulation involves FAS-ligand-", FASmediated T cell apoptosis, 2012, pp.10, 544~555
  36. Milosavljevic N, "Mesenchymal stem cells attenuate acute liver injury by altering ratio between interleukin 17 producing and regulatory natural killer T cells", Liver Transpl, 23, pp.1040~1050 (2017)
  37. Zhao X, "Combined treatment with MSC transplantation and neutrophil depletion ameliorates D-GalN", LPS-induced acute liver failure in rats, 2016, pp.40, 730~738
  38. Zhu X, "Effects of transplanted bonemarrow-derived mesenchymal stem cells in animal models of acute hepatitis", Cell Tissue Res, 351, pp.477~486 (2013)
  39. Wang JL, "Mesenchymal stem cells ameliorate lipid metabolism through reducing mitochondrial damage of hepatocytes in the treatment of posthepatectomy liver failure", Cell Death Dis, 12, pp.111~ (2021)
  40. Ma HC, "Interleukin-10 contributes to therapeutic effect of mesenchymal stem cells for acute liver failure via signal transducer and activator of transcription 3 signaling pathway", Chin Med J(Engl), 129, pp.967~975 (2016)
  41. Wang P, "Mesenchymal stem cells protect against acetaminophen hepatotoxicity by secreting regenerative cytokine hepatocyte growth factor", Stem Cell Res Ther, 13, pp.94~ (2022)
  42. Liu Y, "Prostaglandin E2 secreted by mesenchymal stem cells protects against acute liver failure via enhancing hepatocyte proliferation", FASEB J, 33, pp.2514~2525 (2019)
  43. Wang S, "Tumor necrosis factor-inducible gene 6 promotes liver regeneration in mice with acute liver injury", Stem Cell Res Ther, 6, pp.20~ (2015)
  44. Zhang ZH, "Mesenchymal stem cells increase expression of heme oxygenase-1 leading to anti-inflammatory activity in treatment of acute liver failure", Stem Cell Res Ther, 8, pp.70~ (2017)
  45. Wang Y, "Mesenchymal stem cells increase heme oxygenase 1-activated autophagy in treatment of acute liver failure", Biochem Biophys Res Commun, 508, pp.682~689 (2019)
  46. van Poll D, "Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo", Hepatology, 47, pp.1634~1643 (2008)
  47. Huang B, "Mesenchymal stem cells and their secreted molecules predominantly ameliorate fulminant hepatic failure and chronic liver fibrosis in mice respectively", J Transl Med, 14, pp.45~ (2016)
  48. Parekkadan B, "Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure", PLoS One, 2, pp.e941~ (2007)
  49. Hade MD, "Mesenchymal stem cell-derived exosomes : applications in regenerative medicine", Cells, 10, pp.1959~ (2021)
  50. Damania A, "Mesenchymal stromal cell-derived exosome-rich fractionated secretome confers a hepatoprotective effect in liver injury", Stem Cell Res Ther, 9, pp.31~ (2018)
  51. Zhao S, "Bone marrow mesenchymal stem cellderived exosomes attenuate D-GaIN", LPS-induced hepatocyte apoptosis by activating autophagy in vitro, 2019, pp.13, 2887~2897
  52. Chen L, "Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure", Stem Cell Res Ther, 8, pp.9~ (2017)
  53. Wu HY, "Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acetaminophen-induced acute liver failure through activating ERK and IGF-1R", PI3K, J Pharmacol Sci, pp.2021, 147[DOI]
  54. Liu Y, "AMSC-derived exosomes alleviate lipopolysaccharide", d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP, EBioMedicine, pp.2018, 36[DOI]
  55. Shao M, "Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate IL-6-induced acute liver injury through miR-455-3p", Stem Cell Res Ther, 11, pp.37~ (2020)
  56. Wei W, "Mesenchymal stem cell-derived exosomes : a promising biological tool in nanomedicine", Front Pharmacol, 11, pp.590470~ (2021)
  57. Phinney DG, "Concise review : MSC-derived exosomes for cell-free therapy", Stem Cells, 35, pp.851~858 (2017)
  58. Deng C, "Up-regulation of CXCR4 in rat umbilical mesenchymal stem cells induced by serum from rat with acute liver failure promotes stem cells migration to injured liver tissue", Mol Cell Biochem, 396, pp.107~116 (2014)
  59. Ma HC, "Targeted migration of mesenchymal stem cells modified with CXCR4 to acute failing liver improves liver regeneration", World J Gastroenterol, 20, pp.14884~14894 (2014)
  60. Wang K, "Overexpression of c-Met in bone marrow mesenchymal stem cells improves their effectiveness in homing and repair of acute liver failure", Stem Cell Res Ther, 8, pp.162~ (2017)
  61. Xu R, "CCR2-overexpressing mesenchymal stem cells targeting damaged liver enhance recovery of acute liver failure", Stem Cell Res Ther, 13, pp.55~ (2022)
  62. Yu Y, "HNF4α overexpression enhances the therapeutic potential of umbilical cord mesenchymal stem", stromal cells in mice with acute liver failure, 2022, pp.596, 3176~3190
  63. Wang W, "Interleukin-35 gene-modified mesenchymal stem cells protect concanavalin A-induced fulminant hepatitis by decreasing the interferon gamma level", Hum Gene Ther, 29, pp.234~241 (2018)
  64. Tang Y, "Therapeutic potential of HGF-expressing human umbilical cord mesenchymal stem cells in mice with acute liver failure", Int J Hepatol, 2016, pp.5452487~ (2016)
  65. Zheng YB, "Amniotic-fluid-derived mesenchymal stem cells overexpressing interleukin-1receptor antagonist improve fulminant hepatic failure", PLoS One, 7, pp.e41392~ (2012)
  66. Yeon Ji Chae, "The Use of Foxa2-Overexpressing Adipose Tissue-Derived Stem Cells in a Scaffold System Attenuates Acute Liver Injury", Gut and Liver, 13(4), pp.450~460 (2019), 거트앤리버 소화기연관학회협의회[DOI]
  67. Chen H, "VEGF165 genemodified human umbilical cord blood mesenchymal stem cells protect against acute liver failure in rats", J Gene Med, 23, pp.e3369~ (2021)
  68. Zeng W, "Antioxidant treatment enhances human mesenchymal stem cell anti-stress ability and therapeutic efficacy in an acute liver failure model", Sci Rep, 5, pp.11100~ (2015)
  69. Nie H, "IL-1β pretreatment improves the efficacy of mesenchymal stem cells on acute liver failure by enhancing CXCR4 expression", Stem Cells Int, 2020, pp.1498315~ (2020)
  70. Zhang S, "Pretreatment of exosomes derived from hUCMSCs with TNF-α ameliorates acute liver failure by inhibiting the activation of NLRP3 in macrophage", Life Sci, 246, pp.117401~ (2020)
  71. Zheng Y, "Serum from acute-onchronic liver failure patients may affect mesenchymal stem cells transplantation by impairing the immunosuppressive function of cells", J Clin Transl Hepatol, 9, pp.503~513 (2021)
  72. Chen D, "Menstrual blood-derived mesenchymal stem cells attenuate inflammation and improve the mortality of acute liver failure combining with A2AR agonist in mice", J Gastroenterol Hepatol, 36, pp.2619~2627 (2021)
  73. Sang JF, "Combined mesenchymal stem cell transplantation and interleukin-1 receptor antagonism after partial hepatectomy", World J Gastroenterol, 22, pp.4120~4135 (2016)
  74. Chen H, "Therapeutic effect of human umbilical cord blood mesenchymal stem cells combined with G-CSF on rats with acute liver failure", Biochem Biophys Res Commun, 517, pp.670~676 (2019)
  75. Zhu CH, "Adult stem cell transplantation combined with conventional therapy for the treatment of end-stage liver disease : a systematic review and meta-analysis", Stem Cell Res Ther, 12, pp.558~ (2021)
  76. Xu WX, "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, pp.4130757~ (2019)
  77. Cao H, "Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure", BMC Med, 10, pp.56~ (2012)
  78. He Y, "Human umbilical cord-derived mesenchymal stem cells improve the function of liver in rats with acute-on-chronic liver failure via downregulating Notch and Stat1", Stat3 signaling, 2021, pp.12, 396~
  79. Ryu KH, "Tonsil-derived mesenchymal stem cells alleviate concanavalin A-induced acute liver injury", Exp Cell Res, 326, pp.143~154 (2014)
  80. Salomone F, "Efficacy of adipose tissue-mesenchymal stem cell transplantation in rats with acetaminophen liver injury", Stem Cell Res, 11, pp.1037~1044 (2013)
  81. Shi D, "Quantitative evaluation of human bone mesenchymal stem cells rescuing fulminant hepatic failure in pigs", Gut, 66, pp.955~964 (2017)
  82. Teshima T, "Allogenic adipose tissue-derived mesenchymal stem cells ameliorate acute hepatic injury in dogs", Stem Cells Int, 2017, pp.3892514~ (2017)
  83. Zare H, "Bone marrow or adipose tissue mesenchymal stem cells : comparison of the therapeutic potentials in mice model of acute liver failure", J Cell Biochem, 119, pp.5834~5842 (2018)
  84. Li S, "Mesenchymal stem cells derived from different perinatal tissues donated by same donors manifest variant performance on the acute liver failure model in mouse", Stem Cell Res Ther, 13, pp.231~ (2022)
  85. Zheng S, "Transplantation of umbilical cord mesenchymal stem cells via different routes in rats with acute liver failure", Int J Clin Exp Pathol, 8, pp.15854~15862 (2015)
  86. Putra A, "Intravenous administration is the best route of mesenchymal stem cells migration in improving liver function enzyme of acute liver failure", Folia Med(Plovdiv), 62, pp.52~58 (2020)
  87. Sun L, "Bone mesenchymal stem cell transplantation via four routes for the treatment of acute liver failure in rats", Int J Mol Med, 34, pp.987~996 (2014)
  88. Sang JF, "Intraportal mesenchymal stem cell transplantation prevents acute liver failure through promoting cell proliferation and inhibiting apoptosis", Hepatobiliary Pancreat Dis Int, 15, pp.602~611 (2016)
  89. Jiang Ting, "Application of Bone Marrow Mesenchymal Stem Cells Effectively Eliminates Endotoxemia to Protect Rat from Acute Liver Failure Induced by Thioacetamide", 조직공학과 재생의학, 19(2), pp.403~415 (2022), 한국조직공학과 재생의학회[DOI]
  90. Liu Z, "Human umbilical cord mesenchymal stromal cells rescue mice from acetaminophen-induced acute liver failure", Cytotherapy, 16, pp.1207~1219 (2014)
  91. Lin BL, "Allogeneic bone marrowderived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure : a randomized controlled trial", Hepatology, 66, pp.209~219 (2017)
  92. Peng L, "Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B : short-term and long-term outcomes", Hepatology, 54, pp.820~828 (2011)
  93. Jia Y, "Enhanced therapeutic effects of umbilical cord mesenchymal stem cells after prolonged treatment for HBV-related liver failure and liver cirrhosis", Stem Cell Res Ther, 11, pp.277~ (2020)
  94. Zhang K, "The impact of recipient age on the effects of umbilical cord mesenchymal stem cells on HBV-related acute-on-chronic liver failure and liver cirrhosis", Stem Cell Res Ther, 12, pp.466~ (2021)

관련 논문AI추천

Mesenchymal Stem Cells for the Treatment of Liver Disease: Present and Perspectives엄영우, Moon Young Kim, Seong Hee Kang, Soon Koo Baik거트앤리버 소화기연관학회협의회 · Gut and Liver2020 · 제14권 제3호The development of mesenchymal stem cell therapy in the present, and the perspective of cell-free therapy in the futureAtsunori Tsuchiya, Shuji Terai, Yusuke Watanabe대한간학회 · Clinical and Molecular Hepatology2021 · 제27권 제1호Stem cell exosomes: new hope and future potential for relieving liver fibrosisChong Jin, Hao Jiang, Jinggang Mo, Kunpeng Wang, Lihua Li, Yongjie Liu, Zhiyong Weng대한간학회 · Clinical and Molecular Hepatology2025 · 제31권 제2호Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis권상옥, 김문영, 백순구, 장윤옥, 전백규대한간학회 · Clinical and Molecular Hepatology2015 · 제21권 제2호Mesenchymal Stem Cell-derived Exosomes: Applications in Cell-free Therapy김진관, 허준석대한임상검사과학회 · 대한임상검사과학회지2018 · 제50권 제4호The Use of Foxa2-Overexpressing Adipose Tissue-Derived Stem Cells in a Scaffold System Attenuates Acute Liver InjuryDae Won Jun, Hyeon Tae Kang, Jai Sun Lee, Jin Ho Lee, Kiseok Jang, Waqar Khalid Saeed, Yeon Ji Chae거트앤리버 소화기연관학회협의회 · Gut and Liver2019 · 제13권 제4호

이 간행물의 다른 논문 (18건)

Should All Undifferentiated Early Gastric Cancer Patients Undergoing Noncurative Endoscopic Resection Be Sent to the Operating Room?Kim Albert C., Kim Jung-Wookpp. 665-667Is Tegoprazan-Based Triple Therapy Effective in Regions with High Rates of Clarithromycin Resistance?최현호pp. 668-669Pretransplant Frailty on Postoperative Morbidity and Mortality after Liver Transplantation: Bystander or Upstander?Choi Won-Mookpp. 670-671Evaluating the Self-Expandable Metal Stents Placement in Malignant Biliary Obstruction: A Deeper DivePark Se Woo, Lee Kyong Joopp. 672-673Optimizing Helicobacter pylori Treatment: An Updated Review of Empirical and Susceptibility Test-Based TreatmentsIshibashi Fumiaki, Nagai Mizuki, Mochida Kentaro, Morishita Tetsuo, Suzuki Shopp. 684-697
원문 보기