Role of Liver Progenitor Cell in Liver Regeneration：Cellular Cross-Talks and Signals

doi:10.1007/s12204-015-1615-x

摘要/Abstract

摘要： The liver is well known for its ability to regenerate in response to injury. After partial hepatectomy and some chemicals induced acute liver injury, existing hepatocytes can expand to repair the liver function. While adult liver stem/progenitor cells (LPCs) are evoked and differentiate into functional hepatocytes and cholangiocytes to compensate the damaged liver once hepatocyte proliferation is severely impaired. A number of evidences suggest that adjacent hepatic stellate cells (HSCs) or invading leukocytes may be involved in LPCs directed regeneration through governning two major events including fibrogenic and inflammatory responses respectively or simultaneously. As such, a microenvironment (or “niche”) composed of different cell sources or factors presents diversity, which eventually mediates LPCs response to biliary or hepatocellular regeneration. This mini review aims at summarizing the latest development on the roles of HSCs, macrophages and lymphocytes as well as corresponding signaling pathways in liver progenitor cells mediated biliary and hepatocellular regeneration, and discussing therapeutic potential of liver progenitor cells in hepatic diseases.

关键词: liver stem/progenitor cell (LPCs), liver regeneration, hepatic stellate cells (HSCs), macrophages, lymphocytes, cellular cross talks, liver cell transplantation

Abstract: The liver is well known for its ability to regenerate in response to injury. After partial hepatectomy and some chemicals induced acute liver injury, existing hepatocytes can expand to repair the liver function. While adult liver stem/progenitor cells (LPCs) are evoked and differentiate into functional hepatocytes and cholangiocytes to compensate the damaged liver once hepatocyte proliferation is severely impaired. A number of evidences suggest that adjacent hepatic stellate cells (HSCs) or invading leukocytes may be involved in LPCs directed regeneration through governning two major events including fibrogenic and inflammatory responses respectively or simultaneously. As such, a microenvironment (or “niche”) composed of different cell sources or factors presents diversity, which eventually mediates LPCs response to biliary or hepatocellular regeneration. This mini review aims at summarizing the latest development on the roles of HSCs, macrophages and lymphocytes as well as corresponding signaling pathways in liver progenitor cells mediated biliary and hepatocellular regeneration, and discussing therapeutic potential of liver progenitor cells in hepatic diseases.

Key words: liver stem/progenitor cell (LPCs), liver regeneration, hepatic stellate cells (HSCs), macrophages, lymphocytes, cellular cross talks, liver cell transplantation

中图分类号:

R 392.12

CHEN Li-li (陈黎黎), ZHANG Qian-fei (张倩飞), KONG Xiao-ni*(孔晓妮). Role of Liver Progenitor Cell in Liver Regeneration：Cellular Cross-Talks and Signals[J]. 上海交通大学学报（英文版）, 2015, 20(2): 251-256.

CHEN Li-li (陈黎黎), ZHANG Qian-fei (张倩飞), KONG Xiao-ni*(孔晓妮). Role of Liver Progenitor Cell in Liver Regeneration：Cellular Cross-Talks and Signals[J]. Journal of shanghai Jiaotong University (Science), 2015, 20(2): 251-256.

参考文献

[1] Kang L-I, Mars W M, Michalopoulos G K. Signals and cells involved in regulating liver regeneration[J]. Cells, 2012, 1(4): 1261-1292.
[2] Gao B, Jeong W, Tian Z. Liver: An organ with predominant innate immunity [J]. Hepatology, 2008,47(2): 729-736.
[3] Fausto N. Liver regeneration and repair: Hepatocytes,progenitor cells, and stem cells [J]. Hepatology,2004, 39(6): 1477-1487.
[4] Fausto N, Campbell J S. The role of hepatocytes and oval cells in liver regeneration and repopulation[J]. Mechanisms of Development, 2003, 120(1): 117-130.
[5] Itoh T, Miyajima A. Liver regeneration by stem/progenitor cells [J]. Hepatology, 2014, 59(4):1617-1626.
[6] Theise N D, Saxena R, Portmann B C, et al. The canals of hering and hepatic stem cells in humans [J].Hepatology, 1999, 30(6): 1425-1433.
[7] Lowes K N, Croager E J, Olynyk J K, et al. Oval cell-mediated liver regeneration: Role of cytokines and growth factors[J]. Journal of Gastroenterology and Hepatology, 2003, 18(1): 4-12.
[8] Markiewski M M, Deangelis R A, Lambris J D.Liver inflammation and regeneration: Two distinct biological phenomena or parallel pathophysiologic processes?[J]. Molecular Immunology, 2006, 43(1-2): 45-56.
[9] Morrison S J, Spradling A C. Stem cells and niches: Mechanisms that promote stem cell maintenance throughout life [J]. Cell, 2008, 132(4): 598-611.
[10] Petersen B E. Hepatic “stem” cells: Coming full circle [J]. Blood Cells, Molecules, and Diseases, 2001,27(3): 590-600.
[11] Boulter L, Govaere O, Bird T G, et al.Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease[J]. Nature Medicine, 2012, 18(4): 572-579.
[12] Tee L B, Kirilak Y, Huang W H, et al. Differentiation of oval cells into duct-like cells in preneoplastic liver of rats placed on a choline-deficient diet supplemented with ethionine [J]. Carcinogenesis, 1994,15(12): 2747-2756.
[13] Oh S,Witek R P, Bae S, et al. Bone marrow–derived hepatic oval cells differentiate into hepatocytes in 2-acetylaminouorene/partial hepatectomy-induced liver regeneration [J]. Gastroenterology, 2007, 132(3): 1077-1087.
[14] Laishes B A, Rolfe P B. Search for endogenous liver colony-forming units in F344 rats given a two-thirds hepatectomy during short-term feeding of 2-acetylaminofluorene [J]. Cancer Reasearch, 1981,41(5): 1731-1741.
[15] Williams M J, Clouston A D, Forbes S J. Links between hepatic fibrosis, ductular reaction, and progenitor[J]. Gastroenterology, 2014, 146(2): 349-356.
[16] Lemire J M, Shiojiri N, Fausto N. Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine [J]. American Journal of Pathology, 1991, 139(3): 535-552.
[17] Yin L, Lynch D, Sell S. Participation of different cell types in the restitutive response of the rat liver to periportal injury induced by allyl alcohol [J]. Journal of Hepatology, 1999, 31: 497-507.
[18] Akhurst B, Croager E J, Farley-Roche C A, et al. A modified choline-deficient, ethioninesupplemented diet protocol effectively induces oval cells in mouse liver [J]. Hepatology, 2001, 34(3): 519-522.
[19] Strick-Marchand H, Masse G X, Weiss M C,et al. Lymphocytes support oval cell-dependent liver regeneration [J]. The Journal of Immunology, 2008,181(4): 2764-2771.
[20] Feng D, Kong X, Weng H, et al. Interleukin-22 promotes proliferation of liver stem/progenitor cells in mice and patients with chronic hepatitis B virus infection[J]. Gastroenterology, 2012, 143(1): 188-198.
[21] Wang X, Foster M, Al-Dhalimy M, et al. The origin and liver repopulating capacity of murine [J]. Proceedings of the National Academy of Sciences of the United States of America, 2003, 100(Sup 1): 11881-11888.
[22] Weng H, Feng D, Radaeva S, et al. Interferongamma inhibits liver progenitor cell proliferation in HBV-infected patients and in 3, 5-diethoxycarbonyl-1,4-dihydrocollidine diet-fed mice [J]. Journal of Hepatology,2013, 59(4): 738-745.
[23] Rosenberg D, Ilic Z, Yin L, et al. Proliferation of hepatic lineage cells of normal C57BL and interleukin-6 knockout mice after cocaine-induced periportal injury[J]. Hepatology, 2000, 31(4): 948-955.
[24] Factor V M, Radaeva S A, Thorgeirsson S S.Origin and fate of oval cells in dipin-induced hepatocarcinogenesis in the mouse [J]. American Journal of Pathology, 1994, 145(2): 409-422.
[25] Endo Y, Zhang M, Yamaji S, et al. Genetic abolishment of hepatocyte proliferation activates hepatic stem cells [J]. PLoS One, 2012, 7(2): e31846.
[26] van Hul N K, Abarca-Quinones J, Sempoux C,et al. Relation between liver progenitor cell expansion and extracellular matrix deposition in a CDE-induced murine model of chronic liver injury [J]. Hepatology,2009, 49(5): 1625-1635.
[27] Tirnitz-Parker J E, Olynyk J K, Ramm G A. Role of TWEAK in co-regulating liver progenitor cell and fibrogenic responses [J]. Hepatology, 2014, 59(3): 1198-1201.
[28] Best J, Dolle L, Manka P, et al. Role of liver progenitors in acute liver injury [J]. Frontiers in Physiology,2013, 4: 258.1-8.
[29] Kordes C, H¨aussinger D. Hepatic stem cell niches[J]. The Journal of Clinical Investigation, 2013,123(5): 1874-1880.
[30] Chobert M-N, Couchie D, Fourcot A, et al. Liver precursor cells increase hepatic fibrosis induced by chronic carbon tetrachloride intoxication in rats [J].Laboratory Investigation, 2012, 92(1): 135-150.
[31] Ishikawa T, Factor V M, Marquardt J U, et al.Hepatocyte growth factor/c-Met signaling is required for stem-cell–mediated liver regeneration in mice [J].Hepatology, 2012, 55(4): 1215-1226.
[32] Issa R, Zhou X, Trim N, et al. Mutation in collagen-1 that confers resistance to the action of collagenase results in failure of recovery from CCl4 -induced liver fibrosis, persistence of activated hepatic stellate cells, and diminished hepatocyte regeneration [J]. The FASEB Journal, 2003, 17(1): 47-49.
[33] Lorenzini S, Bird T G, Boulter L, et al. Characterization of a stereotypical cellular and extracellular adult liver progenitor cell niche in rodents and diseased human liver [J]. Gut, 2010, 59(5): 645-654.
[34] Kallis Y N, Robson A J, Fallowfield J A, et al.Remodelling of extracellular matrix is a requirement for the hepatic progenitor cell response [J]. Gut, 2011,60(4): 525-533.
[35] Seki E, Minicis S D, Osterreicher C H, et al.TLR4 enhances TGF-β signaling and hepatic fibrosis[J]. Nature Medicine, 2007, 13(11): 1324-1332.
[36] Jakubowski A, Ambrose C, Parr M, et al.TWEAK induces liver progenitor cell proliferation [J]. The Journal of Clinical Investigation, 2005, 115(9): 2330-2340.
[37] Tirnitz-Parker J E, Viebahn C S, Jakubowski A,et al. Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells [J]. Hepatology,2010, 52(1): 291-302.
[38] Viebahn C S, Benseler V, Holz L E, et al. Invading macrophages play a major role in the liver progenitor cell response to chronic liver injury [J]. Journal of Hepatology, 2010, 53(3): 500-507.
[39] Hines I N, Kremer M, Isayama F, et al. Impaired liver regeneration and increased oval cell numbers following T cell-mediated hepatitis [J]. Hepatology, 2007,46(1): 229-241.
[40] Sun R, Gao B. Negative regulation of liver regeneration by innate immunity (natural killer cells/interferon-r) [J]. Gastroenterology, 2004, 127(5):1525-1539.
[41] Witte E, Witte K, Warszawska K, et al.Interleukin-22: A cytokine produced by T, NK and NKT cell subsets, with importance in the innate immune defense and tissue protection [J]. Cytokine & Growth Factor Reviews, 2010, 21(5): 365-379.
[42] Kong X, Feng D, Mathews S, et al. Hepatoprotective and anti-fibrotic functions of interleukin-22: Therapeutic potential for the treatment of alcoholic liver disease [J]. Journal of Gastroenterology and Hepatology,2013, 28(Sup 1): 56-60.
[43] Kong X, Feng D, Wang H, et al. Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice [J]. Hepatology, 2012, 56(3): 1150-1159.
[44] Asgari S, Pournasr B, Salekdeh G H, et al. Induced pluripotent stem cells: A new era for hepatology[J]. Journal of Hepatology, 2010, 53(4): 738-751.
[45] Kisseleva T, Gigante E, Brenner D A. Recent advances in liver stem cell therapy [J]. Current Opinion in Gastroenterology, 2010, 26(4): 395-402.
[46] Yu B, He Z, You P, et al. Reprogramming fibroblasts into bipotential hepatic stem cells by defined factors[J]. Cell Stem Cell, 2013, 13(3): 328-340.