中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 4
Apr.  2023
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2023  >  39(4): 986-992

Advances in in vitro induction of hepatocyte-like cells and the application of small-molecule compounds in inducing hepatocyte-like cells

DOI: 10.3969/j.issn.1001-5256.2023.04.037

  • Fujian Key Laboratory of Development and Neurobiology, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China

Research funding:

Natural Science Foundation of Fujian Province (2020J05038);

Fujian Education Department (JAT190090)

More Information
  • Corresponding author: TANG Wei, 40720007@qq.com (ORCID: 0000-0001-8841-4125)
  • Received Date: 2022-09-05
  • Accepted Date: 2022-10-12
  • Published Date: 2023-04-20
    Abstract
  • The induction of hepatocyte-like cells (HLCs) in vitro is one of the effective ways to obtain a large number of useful hepatocyte, and these HLCs can be used in disease modeling, drug design, and toxicological evaluation. At present, the induction of HLCs in vitro is mainly achieved by introducing exogenous transcription factors, cytokines or small-molecule compounds. Since small-molecule compounds have the advantages of structural diversity, controllable time and dose, and convenient and safe operation, scientists are devoted to screening out the small-molecule compounds to replace exogenous transcription factors and cytokines, and such compounds have a promising application prospect in the field of regenerative medicine. This article reviews the studies on the in vitro induction of HLCs from pluripotent stem cells and other adult stem cells and summarizes the application of small-molecule compounds in the in vitro induction of HLCs, in order to provide ideas and references for the in vitro induction of HLCs.

     

    • FullText(HTML)
  • loading
    • References(51)
  • [1]
    LI Y, YANG X, PLUMMER R, et al. Human pluripotent stem cell-derived hepatocyte-like cells and organoids for liver disease and therapy[J]. Int J Mol Sci, 2021, 22(19): 10471. DOI: 10.3390/ijms221910471.
    [2]
    FAN Q, LI Z. Liver transplantation for acute-on-chronic liver failure[J]. Ogran Transplant, 2022, 13(3): 333-337. DOI: 10.3969/j.issn.1674-7445.2022.03.008.

    范祺, 李照. 慢加急性肝衰竭的肝移植治疗[J]. 器官移植, 2022, 13(3): 333-337. DOI: 10.3969/j.issn.1674-7445.2022.03.008.
    [3]
    XIA Q, SHA M. Progress and prospect of living donor liver transplantation[J]. Chin J Dig Surg, 2022, 21(1): 39-42. DOI: 10.3760/cma.j.cn115610-20211205-00622.

    夏强, 沙朦. 活体肝移植的进展与展望[J]. 中华消化外科杂志, 2022, 21(1): 39-42. DOI: 10.3760/cma.j.cn115610-20211205-00622.
    [4]
    LUCE E, MESSINA A, DUCLOS-VALLÉE JC, et al. Advanced techniques and awaited clinical applications for human pluripotent stem cell differentiation into hepatocytes[J]. Hepatology, 2021, 74(2): 1101-1116. DOI: 10.1002/hep.31705.
    [5]
    MESSINA A, LUCE E, HUSSEIN M, et al. Pluripotent-stem-cell-derived hepatic cells: hepatocytes and organoids for liver therapy and regeneration[J]. Cells, 2020, 9(2): 420. DOI: 10.3390/cells9020420.
    [6]
    LIU JT, LAMPRECHT MP, DUNCAN SA. Using human induced pluripotent stem cell-derived hepatocyte-like cells for drug discovery[J]. J Vis Exp, 2018, 135: 57194. DOI: 10.3791/57194.
    [7]
    DEGUCHI S, TAKAYAMA K, MIZUGUCHI H. Generation of human induced pluripotent stem cell-derived hepatocyte-like cells for cellular medicine[J]. Biol Pharm Bull, 2020, 43(4): 608-615. DOI: 10.1248/bpb.b19-00740.
    [8]
    ROMBAUT M, BOECKMANS J, RODRIGUES RM, et al. Direct reprogramming of somatic cells into induced hepatocytes: Cracking the Enigma code[J]. J Hepatol, 2021, 75(3): 690-705. DOI: 10.1016/j.jhep.2021.04.048.
    [9]
    XIE Y, YAO J, JIN W, et al. Induction and maturation of hepatocyte-like cells in vitro: focus on technological advances and challenges[J]. Front Cell Dev Biol, 2021, 9: 765980. DOI: 10.3389/fcell.2021.765980.
    [10]
    TOBA Y, DEGUCHI S, MIMURA N, et al. Comparison of commercially available media for hepatic differentiation and hepatocyte maintenance[J]. PLoS One, 2020, 15(2): e0229654. DOI: 10.1371/journal.pone.0229654.
    [11]
    TAKAGI C, YAGI H, HIEDA M, et al. Mesenchymal stem cells contribute to hepatic maturation of human induced pluripotent stem cells[J]. Eur Surg Res, 2017, 58(1-2): 27-39. DOI: 10.1159/000448516.
    [12]
    SGODDA M, DAI Z, ZWEIGERDT R, et al. A scalable approach for the generation of human pluripotent stem cell-derived hepatic organoids with sensitive hepatotoxicity features[J]. Stem Cells Dev, 2017, 26(20): 1490-1504. DOI: 10.1089/scd.2017.0023.
    [13]
    BOON R, KUMAR M, TRICOT T, et al. Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines[J]. Nat Commun, 2020, 11(1): 1393. DOI: 10.1038/s41467-020-15058-6.
    [14]
    BUSHWELLER L, ZHAO Y, ZHANG F, et al. Generation of human pluripotent stem cell-derived polarized hepatocytes[J]. Curr Protoc, 2022, 2(1): e345. DOI: 10.1002/cpz1.345.
    [15]
    DAO THI VL, WU X, BELOTE RL, et al. Stem cell-derived polarized hepatocytes[J]. Nat Commun, 2020, 11(1): 1677. DOI: 10.1038/s41467-020-15337-2.
    [16]
    CHEN YF, TSENG CY, WANG HW, et al. Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol[J]. Hepatology, 2012, 55(4): 1193-1203. DOI: 10.1002/hep.24790.
    [17]
    RAMLI M, LIM YS, KOE CT, et al. Human pluripotent stem cell-derived organoids as models of liver disease[J]. Gastroenterology, 2020, 159(4): 1471-1486. e12. DOI: 10.1053/j.gastro.2020.06.010.
    [18]
    WANG S, WANG X, TAN Z, et al. Human ESC-derived expandable hepatic organoids enable therapeutic liver repopulation and pathophysiological modeling of alcoholic liver injury[J]. Cell Res, 2019, 29(12): 1009-1026. DOI: 10.1038/s41422-019-0242-8.
    [19]
    MARSEE A, ROOS F, VERSTEGEN M, et al. Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids[J]. Cell Stem Cell, 2021, 28(5): 816-832. DOI: 10.1016/j.stem.2021.04.005.
    [20]
    CAYO MA, MALLANNA SK, DI FURIO F, et al. A drug screen using human iPSC-derived hepatocyte-like cells reveals cardiac glycosides as a potential treatment for hypercholesterolemia[J]. Cell Stem Cell, 2017, 20(4): 478-489. e5. DOI: 10.1016/j.stem.2017.01.011.
    [21]
    YANG J, WANG Y, ZHOU T, et al. Generation of human liver chimeric mice with hepatocytes from familial hypercholesterolemia induced pluripotent stem cells[J]. Stem Cell Reports, 2017, 8(3): 605-618. DOI: 10.1016/j.stemcr.2017.01.027.
    [22]
    OVEREEM AW, KLAPPE K, PARISI S, et al. Pluripotent stem cell-derived bile canaliculi-forming hepatocytes to study genetic liver diseases involving hepatocyte polarity[J]. J Hepatol, 2019, 71(2): 344-356. DOI: 10.1016/j.jhep.2019.03.031.
    [23]
    KIM D, KIM SB, RYU JL, et al. Human embryonic stem cell-derived Wilson's disease model for screening drug efficacy[J]. Cells, 2020, 9(4): 872. DOI: 10.3390/cells9040872.
    [24]
    WANG Y, WANG H, DENG P, et al. Modeling human nonalcoholic fatty liver disease (NAFLD) with an organoids-on-a-chip system[J]. ACS Biomater Sci Eng, 2020, 6(10): 5734-5743. DOI: 10.1021/acsbiomaterials.0c00682.
    [25]
    MUN SJ, RYU JS, LEE MO, et al. Generation of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids[J]. J Hepatol, 2019, 71(5): 970-985. DOI: 10.1016/j.jhep.2019.06.030.
    [26]
    JING R, CORBETT JL, CAI J, et al. A screen using iPSC-derived hepatocytes reveals NAD+ as a potential treatment for mtDNA depletion syndrome[J]. Cell Rep, 2018, 25(6): 1469-1484. e5. DOI: 10.1016/j.celrep.2018.10.036.
    [27]
    ZABULICA M, JAKOBSSON T, RAVAIOLI F, et al. Gene editing correction of a urea cycle defect in organoid stem cell derived hepatocyte-like cells[J]. Int J Mol Sci, 2021, 22(3): 1217. DOI: 10.3390/ijms22031217.
    [28]
    TSUNODA T, KAKINUMA S, MIYOSHI M, et al. Loss of fibrocystin promotes interleukin-8-dependent proliferation and CTGF production of biliary epithelium[J]. J Hepatol, 2019, 71(1): 143-152. DOI: 10.1016/j.jhep.2019.02.024.
    [29]
    HUANG P, HE Z, JI S, et al. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors[J]. Nature, 2011, 475(7356): 386-389. DOI: 10.1038/nature10116.
    [30]
    HORISAWA K, UDONO M, UENO K, et al. The dynamics of transcriptional activation by hepatic reprogramming factors[J]. Mol Cell, 2020, 79(4): 660-676. e8. DOI: 10.1016/j.molcel.2020.07.012.
    [31]
    YU B, HE ZY, YOU P, et al. Reprogramming fibroblasts into bipotential hepatic stem cells by defined factors[J]. Cell Stem Cell, 2013, 13(3): 328-340. DOI: 10.1016/j.stem.2013.06.017.
    [32]
    HUANG P, ZHANG L, GAO Y, et al. Direct reprogramming of human fibroblasts to functional and expandable hepatocytes[J]. Cell Stem Cell, 2014, 14(3): 370-384. DOI: 10.1016/j.stem.2014.01.003.
    [33]
    INADA H, UDONO M, MATSUDA-ITO K, et al. Direct reprogramming of human umbilical vein- and peripheral blood-derived endothelial cells into hepatic progenitor cells[J]. Nat Commun, 2020, 11(1): 5292. DOI: 10.1038/s41467-020-19041-z.
    [34]
    HOU P, LI Y, ZHANG X, et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds[J]. Science, 2013, 341(6146): 651-654. DOI: 10.1126/science.1239278.
    [35]
    TASNIM F, PHAN D, TOH YC, et al. Cost-effective differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules[J]. Biomaterials, 2015, 70: 115-125. DOI: 10.1016/j.biomaterials.2015.08.002.
    [36]
    ASUMDA FZ, HATZISTERGOS KE, DYKXHOORN DM, et al. Differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules[J]. Differentiation, 2018, 101: 16-24. DOI: 10.1016/j.diff.2018.03.002.
    [37]
    DU C, FENG Y, QIU D, et al. Highly efficient and expedited hepatic differentiation from human pluripotent stem cells by pure small-molecule cocktails[J]. Stem Cell Res Ther, 2018, 9(1): 58. DOI: 10.1186/s13287-018-0794-4.
    [38]
    GUO R, TANG W, YUAN Q, et al. Chemical cocktails enable hepatic reprogramming of mouse fibroblasts with a single transcription factor[J]. Stem Cell Reports, 2017, 9(2): 499-512. DOI: 10.1016/j.stemcr.2017.06.013.
    [39]
    TANG W, GUO R, SHEN SJ, et al. Chemical cocktails enable hepatic reprogramming of human urine-derived cells with a single transcription factor[J]. Acta Pharmacol Sin, 2019, 40(5): 620-629. DOI: 10.1038/s41401-018-0170-z.
    [40]
    LIM KT, LEE SC, GAO Y, et al. Small molecules facilitate single factor-mediated hepatic reprogramming[J]. Cell Rep, 2016, 15(4): 814-829. DOI: 10.1016/j.celrep.2016.03.071.
    [41]
    PANTA W, IMSOONTHORNRUKSA S, YOISUNGNERN T, et al. Enhanced hepatogenic differentiation of human Wharton's Jelly-derived mesenchymal stem cells by using three-step protocol[J]. Int J Mol Sci, 2019, 20(12): 3016. DOI: 10.3390/ijms20123016.
    [42]
    LUO S, AI Y, XIAO S, et al. Functional hit 1 (FH1)-based rapid and efficient generation of functional hepatocytes from human mesenchymal stem cells: a novel strategy for hepatic differentiation[J]. Ann Transl Med, 2021, 9(13): 1087. DOI: 10.21037/atm-21-2829.
    [43]
    CIPRIANO M, CORREIA JC, CAMÕES SP, et al. The role of epigenetic modifiers in extended cultures of functional hepatocyte-like cells derived from human neonatal mesenchymal stem cells[J]. Arch Toxicol, 2017, 91(6): 2469-2489. DOI: 10.1007/s00204-016-1901-x.
    [44]
    KATSUDA T, KAWAMATA M, HAGIWARA K, et al. Conversion of terminally committed hepatocytes to culturable bipotent progenitor cells with regenerative capacity[J]. Cell Stem Cell, 2017, 20(1): 41-55. DOI: 10.1016/j.stem.2016.10.007.
    [45]
    ZHANG K, ZHANG L, LIU W, et al. In vitro expansion of primary human hepatocytes with efficient liver repopulation capacity[J]. Cell Stem Cell, 2018, 23(6): 806-819. e4. DOI: 10.1016/j.stem.2018.10.018.
    [46]
    XU F, LIU J, DENG J, et al. Rapid and high-efficiency generation of mature functional hepatocyte-like cells from adipose-derived stem cells by a three-step protocol[J]. Stem Cell Res Ther, 2015, 6: 193. DOI: 10.1186/s13287-015-0181-3.
    [47]
    KONDO Y, IWAO T, YOSHIHASHI S, et al. Histone deacetylase inhibitor valproic acid promotes the differentiation of human induced pluripotent stem cells into hepatocyte-like cells[J]. PLoS One, 2014, 9(8): e104010. DOI: 10.1371/journal.pone.0104010.
    [48]
    SGODDA M, MOBUS S, HOEPFNER J, et al. Improved hepatic differentiation strategies for human induced pluripotent stem cells[J]. Curr Mol Med, 2013, 13(5): 842-855. DOI: 10.2174/1566524011313050015.
    [49]
    LI W, DING S. Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming[J]. Trends Pharmacol Sci, 2010, 31(1): 36-45. DOI: 10.1016/j.tips.2009.10.002.
    [50]
    ANG LT, TAN A, AUTIO MI, et al. A roadmap for human liver differentiation from pluripotent stem cells[J]. Cell Rep, 2018, 22(8): 2190-2205. DOI: 10.1016/j.celrep.2018.01.087.
    [51]
    WANG ZY, LI WJ, LI QG, et al. A DMSO-free hepatocyte maturation medium accelerates hepatic differentiation of HepaRG cells in vitro[J]. Biomed Pharmacother, 2019, 116: 109010. DOI: 10.1016/j.biopha.2019.109010.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Tables(4)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (399) PDF downloads(46) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return