多能干细胞在肝脏损伤和修复过程中的免疫调节作用

崔丽娜; 韩英

doi:10.3969/j.issn.1001-5256.2014.09.005

多能干细胞在肝脏损伤和修复过程中的免疫调节作用

DOI: 10.3969/j.issn.1001-5256.2014.09.005

崔丽娜,
韩英

第四军医大学西京消化病医院

详细信息

中图分类号: R575.3
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出版历程
- 收稿日期: 2014-06-18
- 出版日期: 2014-09-20

Immunoregulatory effect of multipotent stem cells in liver injury and repair

Cui LiNa,
Han Ying

Xijing Hospital of Digestive Diseases, Fourth Military Medical University

摘要

摘要: 免疫平衡被打破是肝脏发生损伤或纤维化的基础。因此针对肝脏疾病的治疗不仅需要依赖再生医学发挥肝脏的替代功能,还需要依赖于免疫调节手段。肝脏损伤修复的免疫学基础、多能干细胞用于异体移植的免疫学基础,以及干细胞在治疗肝脏疾病中的免疫调节作用的研究进展发现,多能干细胞尤其是间充质干细胞不仅具有低免疫原性和免疫抑制作用,具备了异体移植的免疫学基础,还可通过免疫调节作用,改善肝脏的局部免疫微环境,从而改善免疫反应导致的肝损伤。提示,多能干细胞用于肝脏疾病的治疗不仅可以满足肝脏替代功能的需求,还可以满足免疫调节能力的需求。多能干细胞移植将成为理想的肝脏疾病治疗手段。
- 肝疾病 /
- 多能干细胞 /
- 免疫,细胞 /
- 干细胞移植
Abstract: Immunological imbalance is the foundation for the development of liver damage or fibrosis. Therefore, the treatment of liver diseases not only relies on regenerative medicine for cellular replacement, but also depends on immunoregulation. The immunological basis of liver injury and repair, the immunological basis of multipotent stem cells for allograft, and the research advances in the immunoregulatory effect of stem cells in the treatment of liver diseases demonstrated that multipotent stem cells, especially mesenchymal stem cells, have low immunogenicity and cause immunosuppression, with the immunological basis of allograft; in addition, they can improve the local immune microenvironment of the liver by immunoregulation to reduce the liver injury caused by immune response. It is suggested that multipotent stem cells, which meet the requirements of cellular replacement and immunoregulation in the liver, will become an ideal treatment of liver diseases.
- liver disease /
- multipotent stem cells /
- immunity, cellular /
- stem cell transplantation

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参考文献(47)

[1] GEBLER A, ZABEL O, SELIGER B.The immunomodulatory capacity of mesenchymal stem cells[J].Trends Mol Med, 2012, 18 (2) :128-134.

[2]DEUSE T, STUBBENDORFF M, TANG-QUAN K, et al.Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells[J].Cell Transplant, 2010, 20 (5) :655-667.

[3]KITAZAWA Y, LI XK, XIE L, et al.Bone marrow-derived conventional, but not cloned, mesenchymal stem cells suppress lymphocyte proliferation and prevent graft-versus-host disease in rats[J].Cell Transplant, 2011, 21 (2-3) :581-590.

[4]LUO C, JIA W, WANG K, et al.Human amniotic fluid stem cells suppress PBMC proliferation through IDO and IL-10-dependent pathways[J].Curr Stem Cell Res Ther, 2014, 9 (1) :36-45.

[5] TOBIN LM, HEALY ME, ENGLISH K, et al.Human mesenchymal stem cells suppress donor CD4 (+) T cell proliferation and reduce pathology in a humanized mouse model of acute graft-versus-host disease[J].Clin Exp Immunol, 2013, 172 (2) :333-348.

[6]SVOBODOVA E, KRULOVA M, ZAJICOVA A, et al.The role of mouse mesenchymal stem cells in differentiation of naive T-cells into anti-inflammatory regulatory T-cell or proinflammatory helper T-cell 17 population[J].Stem Cells Dev, 2012, 21 (6) :901-910.

[7]MAKINO Y, YAMAZA H, AKIYAMA K, et al.Immune therapeutic potential of stem cells from human supernumerary teeth[J].J Dent Res, 2013, 92 (7) :609-615.

[8]ZHANG W, GE W, LI C, et al.Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells[J].Stem Cells Dev, 2004, 13 (3) :263-271.

[9] AGGARWAL S, PITTENGER MF.Human mesenchymal stem cells modulate allogeneic immune cell responses[J].Blood, 2005, 105 (4) :1815-1822.

[10] TACKE F, ZIMMERMANN HW.Macrophage heterogeneity in liver injury and fibrosis[J].J Hepatol, 2014, 60 (5) :1090-1096.

[11]FALLOWFIELD JA, MIZUNO M, KENDALL TJ, et al.Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine hepatic fibrosis[J].J Immunol, 2007, 178 (8) :5288-5295.

[12]PELLICORO A, AUCOTT RL, RAMACHANDRAN P, et al.Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP-12) during experimental liver fibrosis[J].Hepatology, 2012, 55 (6) :1965-1975.

[13] IMAMURA M, OGAWA T, SASAGURI Y, et al.Suppression of macrophage infiltration inhibits activation of hepatic stellate cells and liver fibrogenesis in rats[J].Gastroenterology, 2005, 128 (1) :138-146.

[14]THOMAS JA, POPE C, WOJTACHA D, et al.Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function[J].Hepatology, 2011, 53 (6) :2003-2015.

[15]BAECK C, WEHR A, KARLMARK KR, et al.Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury[J].Gut, 2012, 61 (3) :416-426.

[16] MLLER T, BEUTLER C, PICAH, et al.Increased T-helper 2cytokines in bile from patients with IgG4-related cholangitis disrupt the tight junction-associated biliary epithelial cell barrier[J].Gastroenterology, 2013, 144 (5) :1116-1128.

[17]YANG ZL, CHENG K, SUN HG, et al.Changes in peripheral blood Th1 and Th2 cells in rat liver transplantation under different immune statuses[J].Genet Mol Res, 2013, 12 (4) :6939-6946.

[18]HUANG YH, YAN XS, PENG YQ, et al.Changes of Th1/Th2 cells in immunological liver injury[J].Chin Arch Tradit Chin Med, 2005, 23 (7) :1209-1210. (in Chinese) 黄育华, 晏雪生, 彭亚琴, 等.免疫性肝损伤小鼠Th1/Th2细胞的变化[J].中医药学刊, 2005, 23 (7) :1209-1210.

[19]BRENNDRFER ED, BRASS A, KARTHE J, et al.Cleavage of the T cell protein tyrosine phosphatase by the hepatitis C virus nonstructural 3/4A Protease induces a Th1 to Th2 shift reversible by ribavirin therapy[J].J Immunol, 2014, 192 (4) :1671-1680.

[20] ZHU X, UETRECHT J.A novel T (H) 17-type cell is rapidly increased in the liver in response to acetaminophen-induced liver injury:T (H) 17 cells and the innate immune response[J].J Immunotoxicol, 2013, 10 (3) :287-291.

[21] HAMMERICH L, HEYMANN F, TACKE F.Role of IL-17 and Th17cells in liver diseases[J].Clin Dev Immunol, 2011, 2011:345803.

[22]PARK O, WANG H, WENG H, et al.In vivo consequences of liver-specific interleukin-22 expression in mice:Implications for human liver disease progression[J].Hepatology, 2011, 54 (1) :252-261.

[23]HOU L, JIE Z, DESAI M, et al.Early IL-17 production by intrahepatic T cells is important for adaptive immune responses in viral hepatitis[J].J Immunol, 2013, 190 (2) :621-629.

[24] KUMAR V.NKT-cell subsets:promoters and protectors in inflammatory liver disease[J].J Hepatol, 2013, 59 (3) :618-620.

[25]LU L, FENG M, GU J, et al.Restoration of intrahepatic regulatory T cells through MMP-9/13-dependent activation of TGF-beta is critical for immune homeostasis following acute liver injury[J].J Mol Cell Biol, 2013, 5 (6) :369-379.

[26]DIENES HP, DREBBER U.Pathology of immune-mediated liver injury[J].Dig Dis, 2010, 28 (1) :57-62.

[27] TUCKER RM, FELDMAN AG, FENNER EK, et al.Regulatory T cells inhibit Th1 cell-mediated bile duct injury in murine biliary atresia[J].J Hepatol, 2013, 59 (4) :790-796.

[28]am ESCH JS 2nd, KNOEFEL WT, KLEIN M, et al.Portal application of autologous CD133+bone marrow cells to the liver:a novel concept to support hepatic regeneration[J].Stem Cells, 2005, 23 (4) :463-470.

[29]von LTTICHAU I, NOTOHAMIPRODJO M, WECHSELBERGER A, et al.Human adult CD34-progenitor cells functionally express the chemokine receptors CCR1, CCR4, CCR7, CXCR5, and CCR10 but not CXCR4[J].Stem Cells Dev, 2005, 14 (3) :329-336.

[30]LI Q, ZHOU X, SHI Y, et al.In vivo tracking and comparison of the therapeutic effects of MSCs and HSCs for liver injury[J].PLoS One, 2013, 8 (4) :e62363.

[31] WANG J, ZHOU X, CUI L, et al.The significance of CD14+monocytes in peripheral blood stem cells for the treatment of rat liver cirrhosis[J].Cytotherapy, 2010, 12 (8) :1022-1034.

[32]LIN H, XU R, ZHANG Z, et al.Implications of the immunoregulatory functions of mesenchymal stem cells in the treatment of human liver diseases[J].Cell Mol Immunol, 2011, 8 (1) :19-22.

[33] LEE MJ, JUNG J, NA KH, et al.Anti-fibrotic effect of chorionic plate-derived mesenchymal stem cells isolated from human placenta in a rat model of CCl4-injured liver:potential application to the treatment of hepatic diseases[J].J Cell Biochem, 2010, 111 (6) :1453-1463.

[34] TANIMOTO H, TERAI S, TARO T, et al.Improvement of liver fibrosis by infusion of cultured cells derived from human bone marrow[J].Cell Tissue Res, 2013, 354 (3) :717-728.

[35] PAREKKADAN B, van POLL D, MEGEED Z, et al.Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells[J].Biochem Biophys Res Commun, 2007, 363 (2) :247-252.

[36] LIN N, HU K, CHEN S, et al.Nerve growth factor-mediated paracrine regulation of hepatic stellate cells by multipotent mesenchymal stromal cells[J].Life Sci, 2009, 85 (7-8) :291-295.

[37] DU Z, WEI C, CHENG K, et al.Mesenchymal stem cell-conditioned medium reduces liver injury and enhances regeneration in reduced-size rat liver transplantation[J].J Surg Res, 2013, 183 (2) :907-915.

[38] HIGASHIMOTO M, SAKAI Y, TAKAMURA M, et al.Adipose tissue derived stromal stem cell therapy in murine ConA-derived hepatitis is dependent on myeloid-lineage and CD4+T-cell suppression[J].Eur J Immunol, 2013, 43 (11) :2956-2968.

[39]BUSCH SA, HAMILTON JA, HORN KP, et al.Multipotent adult progenitor cells prevent macrophage-mediated axonal dieback and promote regrowth after spinal cord injury[J].J Neurosci, 2011, 31 (3) :944-953.

[40]DAYAN V, YANNARELLI G, BILLIA F, et al.Mesenchymal stromal cells mediate a switch to alternatively activated monocytes/macrophages after acute myocardial infarction[J].Basic Res Cardiol, 2011, 106 (6) :1299-1310.

[41] YLSTALO JH, BARTOSH TJ, COBLE K, et al.Human mesenchymal stem/stromal cells cultured as spheroids are self-activated to produce prostaglandin E2 that directs stimulated macrophages into an anti-inflammatory phenotype[J].Stem Cells, 2012, 30 (10) :2283-2296.

[42]FURUHASHI K, TSUBOI N, SHIMIZU A, et al.Serum-starved adipose-derived stromal cells ameliorate crescentic GN by promoting immunoregulatory macrophages[J].J Am Soc Nephrol, 2013, 24 (4) :587-603.

[43]MATHIAS LJ, KHONG SM, SPYROGLOU L, et al.Alveolar macrophages are critical for the inhibition of allergic asthma by mesenchymal stromal cells[J].J Immunol, 2013, 191 (12) :5914-5924.

[44]ZHENG L, CHU J, SHI Y, et al.Bone marrow-derived stem cells ameliorate hepatic fibrosis by down-regulating interleukin-17[J].Cell Biosci, 2013, 3 (1) :46.

[45] EZQUER M, EZQUER F, RICCA M, et al.Intravenous administration of multipotent stromal cells prevents the onset of non-alcoholic steatohepatitis in obese mice with metabolic syndrome[J].J Hepatol, 2011, 55 (5) :1112-1120.

[46]WANG L, LI J, LIU H, et al.A pilot study of umbilical cord-derived mesenchymal stem cell transfusion in patients with primary biliary cirrhosis[J].J Gastroenterol Hepatol, 2013, 28 (Suppl 1) :85-92.

[47]WANG D, ZHANG H, LIANG J, et al.Effect of allogeneic bone marrow-derived mesenchymal stem cells transplantation in a polyI:C-induced primary biliary cirrhosis mouse model[J].Clin Exp Med, 2011, 11 (1) :25-32.引证本文:CUI LN, HAN Y.Immunoregulatory effect of multipotent stem cells in liver injury and repair[J].J Clin Hepatol, 2014, 30 (9) :855-859. (in Chinese) 崔丽娜, 韩英.多能干细胞在肝脏损伤和修复过程中的免疫调节作用[J].临床肝胆病杂志, 2014, 30 (9) :855-859.

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