1932

Abstract

As medical and pharmacological technology advances, new and complex modalities of disease treatment that are more personalized and targeted are being developed. Often these modalities must be validated in the presence of critical components of the human biological system. Given the incongruencies between murine and human biology, as well as the human-tropism of certain drugs and pathogens, the selection of animal models that accurately recapitulate the intricacies of the human biological system becomes more salient for disease modeling and preclinical testing. Immunodeficient mice engrafted with functional human tissues (so-called humanized mice), which allow for the study of physiologically relevant disease mechanisms, have thus become an integral aspect of biomedical research. This review discusses the recent advancements and applications of humanized mouse models on human immune system and liver humanization in modeling human diseases, as well as how they can facilitate translational medicine.

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2022-02-15
2024-04-22
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Literature Cited

  1. 1. 
    Food Drug Adm 2015. Product Development under the Animal Rule: Guidance for Industry Washington, DC: Food Drug Adm.
  2. 2. 
    Van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S et al. 2010. Can animal models of disease reliably inform human studies?. PLOS Med 7:e1000245
    [Google Scholar]
  3. 3. 
    Wang J, Ioan-Facsinay A, Van der Voort EI, Huizinga TW, Toes RE 2007. Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur. J. Immunol. 37:129–38
    [Google Scholar]
  4. 4. 
    Martín-Fontecha A, Thomsen LL, Brett S, Gerard C, Lipp M et al. 2004. Induced recruitment of NK cells to lymph nodes provides IFN-γ for TH1 priming. Nat. Immunol. 5:1260–65
    [Google Scholar]
  5. 5. 
    Lin S, Lin Y, Nery JR, Urich MA, Breschi A et al. 2014. Comparison of the transcriptional landscapes between human and mouse tissues. PNAS 111:17224–29
    [Google Scholar]
  6. 6. 
    Chen Q, Amaladoss A, Ye W, Liu M, Dummler S et al. 2014. Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells. PNAS 111:1479–84
    [Google Scholar]
  7. 7. 
    Costa VV, Ye W, Chen Q, Teixeira MM, Preiser P et al. 2017. Dengue virus-infected dendritic cells, but not monocytes, activate natural killer cells through a contact-dependent mechanism involving adhesion molecules. mBio 8:e00741-17
    [Google Scholar]
  8. 8. 
    Capasso A, Lang J, Pitts TM, Jordan K, Lieu C et al. 2019. Characterization of immune responses to anti-PD-1 mono and combination immunotherapy in hematopoietic humanized mice implanted with tumor xenografts. J. Immunother. Cancer 7:37
    [Google Scholar]
  9. 9. 
    Norelli M, Camisa B, Barbiera G, Falcone L, Purevdorj A et al. 2018. Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nat. Med. 24:739–48
    [Google Scholar]
  10. 10. 
    Yong KSM, Her Z, Chen Q. 2019. Humanized mouse models for the study of hepatitis C and host interactions. Cells 8:604
    [Google Scholar]
  11. 11. 
    Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV et al. 2013. Genomic responses in mouse models poorly mimic human inflammatory diseases. PNAS 110:3507–12
    [Google Scholar]
  12. 12. 
    Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. 2014. Clinical development success rates for investigational drugs. Nat. Biotechnol. 32:40–51
    [Google Scholar]
  13. 13. 
    McDermott SP, Eppert K, Lechman ER, Doedens M, Dick JE 2010. Comparison of human cord blood engraftment between immunocompromised mouse strains. Blood 116:193–200
    [Google Scholar]
  14. 14. 
    Christianson SW, Greiner DL, Hesselton RA, Leif JH, Wagar EJ et al. 1997. Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice. J. Immunol. 158:3578–86
    [Google Scholar]
  15. 15. 
    Yong KSM, Her Z, Chen Q. 2018. Humanized mice as unique tools for human-specific studies. Arch. Immunol. Ther. Exp. 66:245–66
    [Google Scholar]
  16. 16. 
    Goldman JP, Blundell MP, Lopes L, Kinnon C, Di Santo JP, Thrasher AJ. 1998. Enhanced human cell engraftment in mice deficient in RAG2 and the common cytokine receptor γ chain. Br. J. Haematol. 103:335–42
    [Google Scholar]
  17. 17. 
    Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M et al. 2002. NOD/SCID/γcnull mouse: an excellent recipient mouse model for engraftment of human cells. Blood J. Am. Soc. Hematol. 100:3175–82
    [Google Scholar]
  18. 18. 
    Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X et al. 2005. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2Rγnull mice engrafted with mobilized human hemopoietic stem cells. J. Immunol. 174:6477–89
    [Google Scholar]
  19. 19. 
    Pearson T, Shultz LD, Miller D, King M, Laning J et al. 2008. Non-obese diabetic-recombination activating gene-1 (NOD-Rag 1null) interleukin (IL)-2 receptor common gamma chain (IL 2 rγnull) null mice: a radioresistant model for human lymphohaematopoietic engraftment. Clin. Exp. Immunol. 154:270–84
    [Google Scholar]
  20. 20. 
    Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti J-C et al. 2004. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 304:104–7
    [Google Scholar]
  21. 21. 
    Yuan L, Jiang J, Liu X, Zhang Y, Zhang L et al. 2019. HBV infection-induced liver cirrhosis development in dual-humanized mice with human bone mesenchymal stem cell transplantation. Gut 68:2044–56
    [Google Scholar]
  22. 22. 
    Strick-Marchand H, Dusséaux M, Darche S, Huntington ND, Legrand N et al. 2015. A novel mouse model for stable engraftment of a human immune system and human hepatocytes. PLOS ONE 10:e0119820-e20
    [Google Scholar]
  23. 23. 
    Strowig T, Rongvaux A, Rathinam C, Takizawa H, Borsotti C et al. 2011. Transgenic expression of human signal regulatory protein alpha in Rag2−/−γc−/− mice improves engraftment of human hematopoietic cells in humanized mice. PNAS 108:13218–23
    [Google Scholar]
  24. 24. 
    Jinnouchi F, Yamauchi T, Yurino A, Nunomura T, Nakano M et al. 2020. A human SIRPA knock-in xenograft mouse model to study human hematopoietic and cancer stem cells. Blood 135:1661–72
    [Google Scholar]
  25. 25. 
    Leonard A, Yapundich M, Nassehi T, Gamer J, Drysdale CM et al. 2019. Low-dose busulfan reduces human CD34+ cell doses required for engraftment in c-kit mutant immunodeficient mice. Mol. Ther. 15:430–37
    [Google Scholar]
  26. 26. 
    Nocka K, Tan JC, Chiu E, Chu TY, Ray P et al. 1990. Molecular bases of dominant negative and loss of function mutations at the murine c-kit/white spotting locus: W37, Wv, W41 and W. EMBO J 9:1805–13
    [Google Scholar]
  27. 27. 
    Cosgun Kadriye N, Rahmig S, Mende N, Reinke S, Hauber I et al. 2014. Kit regulates HSC engraftment across the human-mouse species barrier. Cell Stem Cell 15:227–38
    [Google Scholar]
  28. 28. 
    Rahmig S, Kronstein-Wiedemann R, Fohgrub J, Kronstein N, Nevmerzhitskaya A et al. 2016. Improved human erythropoiesis and platelet formation in humanized NSGW41 mice. Stem Cell Rep 7:591–601
    [Google Scholar]
  29. 29. 
    Sippel TR, Radtke S, Olsen TM, Kiem H-P, Rongvaux A. 2019. Human hematopoietic stem cell maintenance and myeloid cell development in next-generation humanized mouse models. Blood Adv 3:268–74
    [Google Scholar]
  30. 30. 
    Danner R, Chaudhari SN, Rosenberger J, Surls J, Richie TL et al. 2011. Expression of HLA class II molecules in humanized NOD.Rag1KO.IL2RgcKO mice is critical for development and function of human T and B cells. PLOS ONE 6:e19826
    [Google Scholar]
  31. 31. 
    Huang J, Li X, Coelho-dos-Reis JGA, Zhang M, Mitchell R et al. 2015. Human immune system mice immunized with Plasmodium falciparum circumsporozoite protein induce protective human humoral immunity against malaria. J. Immunol. Methods 427:42–50
    [Google Scholar]
  32. 32. 
    Weißmüller S, Kronhart S, Kreuz D, Schnierle B, Kalinke U et al. 2016. TGN1412 induces lymphopenia and human cytokine release in a humanized mouse model. PLOS ONE 11:e0149093
    [Google Scholar]
  33. 33. 
    Tan S, Li Y, Xia J, Jin C-H, Hu Z et al. 2017. Type 1 diabetes induction in humanized mice. PNAS 114:10954–59
    [Google Scholar]
  34. 34. 
    Majji S, Wijayalath W, Shashikumar S, Pow-Sang L, Villasante E et al. 2016. Differential effect of HLA class-I versus class-II transgenes on human T and B cell reconstitution and function in NRG mice. Sci. Rep. 6:28093
    [Google Scholar]
  35. 35. 
    Masse-Ranson G, Dusséaux M, Fiquet O, Darche S, Boussand M et al. 2019. Accelerated thymopoiesis and improved T-cell responses in HLA-A2/-DR2 transgenic BRGS-based human immune system mice. Eur. J. Immunol. 49:954–65
    [Google Scholar]
  36. 36. 
    Zeng Y, Liu B, Rubio M-T, Wang X, Ojcius DM et al. 2017. Creation of an immunodeficient HLA-transgenic mouse (HUMAMICE) and functional validation of human immunity after transfer of HLA-matched human cells. PLOS ONE 12:e0173754
    [Google Scholar]
  37. 37. 
    Takahashi T, Katano I, Ito R, Goto M, Abe H et al. 2018. Enhanced antibody responses in a novel NOG transgenic mouse with restored lymph node organogenesis. Front. Immunol. 8:2017–17
    [Google Scholar]
  38. 38. 
    Li Y, Masse-Ranson G, Garcia Z, Bruel T, Kök A et al. 2018. A human immune system mouse model with robust lymph node development. Nat. Methods 15:623–30
    [Google Scholar]
  39. 39. 
    Chen Q, Khoury M, Chen J. 2009. Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice. PNAS 106:21783–88
    [Google Scholar]
  40. 40. 
    Chen Q, Ye W, Jian Tan W, Mei Yong KS, Liu M et al. 2015. Delineation of natural killer cell differentiation from myeloid progenitors in human. Sci. Rep. 5:15118
    [Google Scholar]
  41. 41. 
    Amaladoss A, Chen Q, Liu M, Dummler SK, Dao M et al. 2015. De novo generated human red blood cells in humanized mice support Plasmodium falciparum infection. PLOS ONE 10:e0129825
    [Google Scholar]
  42. 42. 
    Chen Q, He F, Kwang J, Chan JK, Chen J 2012. GM-CSF and IL-4 stimulate antibody responses in humanized mice by promoting T, B, and dendritic cell maturation. J. Immunol. 189:5223–29
    [Google Scholar]
  43. 43. 
    Rathinam C, Poueymirou WT, Rojas J, Murphy AJ, Valenzuela DM et al. 2011. Efficient differentiation and function of human macrophages in humanized CSF-1 mice. Blood 118:3119–28
    [Google Scholar]
  44. 44. 
    Rongvaux A, Willinger T, Takizawa H, Rathinam C, Auerbach W et al. 2011. Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo. PNAS 108:2378–83
    [Google Scholar]
  45. 45. 
    Yu H, Borsotti C, Schickel J-N, Zhu S, Strowig T et al. 2017. A novel humanized mouse model with significant improvement of class-switched, antigen-specific antibody production. Blood 129:959–69
    [Google Scholar]
  46. 46. 
    Herndler-Brandstetter D, Shan L, Yao Y, Stecher C, Plajer V et al. 2017. Humanized mouse model supports development, function, and tissue residency of human natural killer cells. PNAS 114:E9626–E34
    [Google Scholar]
  47. 47. 
    Billerbeck E, Barry WT, Mu K, Dorner M, Rice CM, Ploss A 2011. Development of human CD4+ FoxP3+ regulatory T cells in human stem cell factor–, granulocyte-macrophage colony-stimulating factor–, and interleukin-3–expressing NOD-SCID IL2Rγnull humanized mice. Blood J. Am. Soc. Hematol. 117:3076–86
    [Google Scholar]
  48. 48. 
    Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV et al. 2014. Development and function of human innate immune cells in a humanized mouse model. Nat. Biotechnol. 32:364–72
    [Google Scholar]
  49. 49. 
    Song Y, Rongvaux A, Taylor A, Jiang T, Tebaldi T et al. 2019. A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies. Nat. Commun. 10:366
    [Google Scholar]
  50. 50. 
    Das R, Strowig T, Verma R, Koduru S, Hafemann A et al. 2016. Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice. Nat. Med. 22:1351–57
    [Google Scholar]
  51. 51. 
    Kametani Y, Katano I, Miyamoto A, Kikuchi Y, Ito R et al. 2017. NOG-hIL-4-Tg, a new humanized mouse model for producing tumor antigen-specific IgG antibody by peptide vaccination. PLOS ONE 12:e0179239
    [Google Scholar]
  52. 52. 
    Wunderlich M, Sexton C, Mizukawa B, Mulloy JC 2013. NSGS mice develop a progressive, myeloid cell dependent aplastic anemia and bone marrow failure upon engraftment with human umbilical cord blood CD34+ cells. Blood 122:3716
    [Google Scholar]
  53. 53. 
    Dandri M, Burda MR, Török E, Pollok JM, Iwanska A et al. 2001. Repopulation of mouse liver with human hepatocytes and in vivo infection with hepatitis B virus. Hepatology 33:981–88
    [Google Scholar]
  54. 54. 
    Mercer DF, Schiller DE, Elliott JF, Douglas DN, Hao C et al. 2001. Hepatitis C virus replication in mice with chimeric human livers. Nat. Med. 7:927–33
    [Google Scholar]
  55. 55. 
    Suemizu H, Hasegawa M, Kawai K, Taniguchi K, Monnai M et al. 2008. Establishment of a humanized model of liver using NOD/Shi-scid IL2Rgnull mice. Biochem. Biophys. Res. Commun. 377:248–52
    [Google Scholar]
  56. 56. 
    Strom SC, Davila J, Grompe M. 2010. Chimeric mice with humanized liver: tools for the study of drug metabolism, excretion, and toxicity. Methods Mol. Biol. 640:491–509
    [Google Scholar]
  57. 57. 
    Azuma H, Paulk N, Ranade A, Dorrell C, Al-Dhalimy M et al. 2007. Robust expansion of human hepatocytes in Fah−/−/Rag2−/−/Il2rg−/− mice. Nat. Biotechnol. 25:903–10
    [Google Scholar]
  58. 58. 
    Billerbeck E, Mommersteeg MC, Shlomai A, Xiao JW, Andrus L et al. 2016. Humanized mice efficiently engrafted with fetal hepatoblasts and syngeneic immune cells develop human monocytes and NK cells. J. Hepatol. 65:334–43
    [Google Scholar]
  59. 59. 
    Song Y, Shan L, Gbyli R, Liu W, Strowig T et al. 2021. Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells. Science 371:1019–25
    [Google Scholar]
  60. 60. 
    Hasegawa M, Kawai K, Mitsui T, Taniguchi K, Monnai M et al. 2011. The reconstituted ‘humanized liver’ in TK-NOG mice is mature and functional. Biochem. Biophys. Res. Commun. 405:405–10
    [Google Scholar]
  61. 61. 
    Washburn ML, Bility MT, Zhang L, Kovalev GI, Buntzman A et al. 2011. A humanized mouse model to study hepatitis C virus infection, immune response, and liver disease. Gastroenterology 140:1334–44
    [Google Scholar]
  62. 62. 
    Chen Q, Khoury M, Limmon G, Choolani M, Chan JK, Chen J 2013. Human fetal hepatic progenitor cells are distinct from, but closely related to, hematopoietic stem/progenitor cells. Stem Cells 31:1160–69
    [Google Scholar]
  63. 63. 
    Yong KSM, Keng CT, Tan SQ, Loh E, Chang KT et al. 2016. Human CD34loCD133lo fetal liver cells support the expansion of human CD34hiCD133hi hematopoietic stem cells. Cell. Mol. Immunol. 13:605–14
    [Google Scholar]
  64. 64. 
    Guo J, Li Y, Shan Y, Shu C, Wang F et al. 2018. Humanized mice reveal an essential role for human hepatocytes in the development of the liver immune system. Cell Death Dis 9:667
    [Google Scholar]
  65. 65. 
    Lai F, Wee CYY, Chen Q. 2021. Establishment of humanized mice for the study of HBV. Front. Immunol. 12:638447
    [Google Scholar]
  66. 66. 
    Evren E, Ringqvist E, Tripathi KP, Sleiers N, Rives IC et al. 2021. Distinct developmental pathways from blood monocytes generate human lung macrophage diversity. Immunity 54:259–75.e7
    [Google Scholar]
  67. 67. 
    Gonzalez H, Hagerling C, Werb Z. 2018. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev 32:1267–84
    [Google Scholar]
  68. 68. 
    Kuryk L, Møller A-SW, Jaderberg M. 2019. Combination of immunogenic oncolytic adenovirus ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized A2058 melanoma huNOG mouse model. Oncoimmunology 8:e1532763
    [Google Scholar]
  69. 69. 
    Choi B, Lee JS, Kim SJ, Hong D, Park JB, Lee K-Y 2020. Anti-tumor effects of anti-PD-1 antibody, pembrolizumab, in humanized NSG PDX mice xenografted with dedifferentiated liposarcoma. Cancer Lett 478:56–69
    [Google Scholar]
  70. 70. 
    Meraz IM, Majidi M, Meng F, Shao R, Ha MJ et al. 2019. An improved patient-derived xenograft humanized mouse model for evaluation of lung cancer immune responses. Cancer Immunol. Res. 7:8 https://doi.org/10.1158/2326-6066.CIR-18-0874
    [Crossref] [Google Scholar]
  71. 71. 
    Rosato RR, Dávila-González D, Choi DS, Qian W, Chen W et al. 2018. Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models. Breast Cancer Res 20:108
    [Google Scholar]
  72. 72. 
    Liu WN, Fong SY, Tan WWS, Tan SY, Liu M et al. 2020. Establishment and characterization of humanized mouse NPC-PDX model for testing immunotherapy. Cancers 12:41025
    [Google Scholar]
  73. 73. 
    Zhao Y, Wang J, Liu WN, Fong SY, Shuen TWH et al. 2021. Analysis and validation of human targets and treatments using a hepatocellular carcinoma-immune humanized mouse model. Hepatology 74:1395–410
    [Google Scholar]
  74. 74. 
    Jiang Z, Jiang X, Chen S, Lai Y, Wei X et al. 2017. Anti-GPC3-CAR T cells suppress the growth of tumor cells in patient-derived xenografts of hepatocellular carcinoma. Front. Immunol. 7:690
    [Google Scholar]
  75. 75. 
    Forsberg EMV, Lindberg MF, Jespersen H, Alsén S, Bagge RO et al. 2019. HER2 CAR-T cells eradicate uveal melanoma and T-cell therapy-resistant human melanoma in IL2 transgenic NOD/SCID IL2 receptor knockout mice. Cancer Res 79:899–904
    [Google Scholar]
  76. 76. 
    Moreira D, Sampath S, Won H, White SV, Su Y-L et al. 2021. Myeloid cell–targeted STAT3 inhibition sensitizes head and neck cancers to radiotherapy and T cell–mediated immunity. J. Clin. Investig. 131:2e137001
    [Google Scholar]
  77. 77. 
    Malaney P, Nicosia SV, Davé V. 2014. One mouse, one patient paradigm: new avatars of personalized cancer therapy. Cancer Lett 344:11–12
    [Google Scholar]
  78. 78. 
    Chen Q, Wang J, Liu WN, Zhao Y. 2019. Cancer immunotherapies and humanized mouse drug testing platforms. Transl. Oncol. 12:987–95
    [Google Scholar]
  79. 79. 
    Zhao Y, Shuen TWH, Toh TB, Chan XY, Liu M et al. 2018. Development of a new patient-derived xenograft humanized mouse model to study human-specific tumour microenvironment and immunotherapy. Gut 67:1845–54
    [Google Scholar]
  80. 80. 
    Kaur M, Drake AC, Hu G, Rudnick S, Chen Q et al. 2019. Induction and therapeutic targeting of human NPM1c+ myeloid leukemia in the presence of autologous immune system in mice. J. Immunol. 202:1885–94
    [Google Scholar]
  81. 81. 
    Xia J, Hu Z, Yoshihara S, Li Y, Jin C-H et al. 2016. Modeling human leukemia immunotherapy in humanized mice. EBioMedicine 10:101–8
    [Google Scholar]
  82. 82. 
    Jin C-H, Xia J, Rafiq S, Huang X, Hu Z et al. 2019. Modeling anti-CD19 CAR T cell therapy in humanized mice with human immunity and autologous leukemia. EBioMedicine 39:173–81
    [Google Scholar]
  83. 83. 
    Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A et al. 2006. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N. Engl. J. Med. 355:1018–28
    [Google Scholar]
  84. 84. 
    Attarwala H. 2010. TGN1412: from discovery to disaster. J. Young Pharm. 2:332–36
    [Google Scholar]
  85. 85. 
    Ye C, Yang H, Cheng M, Shultz LD, Greiner DL et al. 2020. A rapid, sensitive, and reproducible in vivo PBMC humanized murine model for determining therapeutic-related cytokine release syndrome. FASEB J 34:12963–75
    [Google Scholar]
  86. 86. 
    Reardon S. 2015. NIH to retire all research chimpanzees. Nature News, Nov. 18. https://doi.org/10.1038/nature.2015.18817
    [Crossref]
  87. 87. 
    Marsden MD. 2020. Benefits and limitations of humanized mice in HIV persistence studies. Retrovirology 17:7
    [Google Scholar]
  88. 88. 
    Nixon CC, Mavigner M, Sampey GC, Brooks AD, Spagnuolo RA et al. 2020. Systemic HIV and SIV latency reversal via non-canonical NF-κB signalling in vivo. Nature 578:160–65
    [Google Scholar]
  89. 89. 
    Sperber HS, Togarrati PP, Raymond KA, Bouzidi MS, Gilfanova R et al. 2020. μ-Lat: a mouse model to evaluate human immunodeficiency virus eradication strategies. FASEB J 34:14615–30
    [Google Scholar]
  90. 90. 
    Salgado M, Martinez-Picado J, Gálvez C, Rodríguez-Mora S, Rivaya B et al. 2020. Dasatinib protects humanized mice from acute HIV-1 infection. Biochem. Pharmacol. 174:113625
    [Google Scholar]
  91. 91. 
    Anthony-Gonda K, Bardhi A, Ray A, Flerin N, Li M et al. 2019. Multispecific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells in a humanized mouse model. Sci. Transl. Med. 11:eaav5685
    [Google Scholar]
  92. 92. 
    Kuhlmann A-S, Haworth KG, Barber-Axthelm IM, Ironside C, Giese MA et al. 2019. Long-term persistence of anti-HIV broadly neutralizing antibody-secreting hematopoietic cells in humanized mice. Mol. Ther. 27:164–77
    [Google Scholar]
  93. 93. 
    Balazs AB, Chen J, Hong CM, Rao DS, Yang L, Baltimore D 2011. Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature 481:81–84
    [Google Scholar]
  94. 94. 
    Sridharan A, Chen Q, Tang KF, Ooi EE, Hibberd ML, Chen J. 2013. Inhibition of megakaryocyte development in the bone marrow underlies dengue virus-induced thrombocytopenia in humanized mice. J. Virol. 87:11648–58
    [Google Scholar]
  95. 95. 
    Coronel-Ruiz C, Gutiérrez-Barbosa H, Medina-Moreno S, Velandia-Romero ML, Chua JV et al. 2020. Humanized mice in dengue research: a comparison with other mouse models. Vaccines 8:39
    [Google Scholar]
  96. 96. 
    Cui L, Hou J, Fang J, Lee YH, Costa VV et al. 2017. Serum metabolomics investigation of humanized mouse model of dengue virus infection. J. Virol. 91:e00386–17
    [Google Scholar]
  97. 97. 
    Bissig KD, Wieland SF, Tran P, Isogawa M, Le TT et al. 2010. Human liver chimeric mice provide a model for hepatitis B and C virus infection and treatment. J. Clin. Investig. 120:924–30
    [Google Scholar]
  98. 98. 
    Lütgehetmann M, Mancke LV, Volz T, Helbig M, Allweiss L et al. 2012. Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation. Hepatology 55:685–94
    [Google Scholar]
  99. 99. 
    Tan-Garcia A, Wai L-E, Zheng D, Ceccarello E, Jo J et al. 2017. Intrahepatic CD206+ macrophages contribute to inflammation in advanced viral-related liver disease. J. Hepatol. 67:490–500
    [Google Scholar]
  100. 100. 
    Tan-Garcia A, Lai F, Yeong JPS, Irac SE, Ng PY et al. 2020. Liver fibrosis and CD206+ macrophage accumulation are suppressed by anti-GM-CSF therapy. JHEP Rep 2:100062
    [Google Scholar]
  101. 101. 
    Zheng Z, Sze CW, Keng CT, Al-Haddawi M, Liu M et al. 2017. Hepatitis C virus mediated chronic inflammation and tumorigenesis in the humanized immune system and liver mouse model. PLOS ONE 12:e0184127
    [Google Scholar]
  102. 102. 
    Keng CT, Sze CW, Zheng D, Zheng Z, Yong KSM et al. 2016. Characterisation of liver pathogenesis, human immune responses and drug testing in a humanized mouse model of HCV infection. Gut 65:1744–53
    [Google Scholar]
  103. 103. 
    Bae KH, Lee F, Xu K, Keng CT, Tan SY et al. 2015. Microstructured dextran hydrogels for burst-free sustained release of PEGylated protein drugs. Biomaterials 63:146–57
    [Google Scholar]
  104. 104. 
    Craig AG, Grau GE, Janse C, Kazura JW, Milner D et al. 2012. The role of animal models for research on severe malaria. PLOS Pathog 8:e1002401
    [Google Scholar]
  105. 105. 
    Jiménez-Díaz MB, Mulet T, Viera S, Gómez V, Garuti H et al. 2009. Improved murine model of malaria using Plasmodium falciparum competent strains and non-myelodepleted NOD-scid IL2Rγnull mice engrafted with human erythrocytes. Antimicrob. Agents Chemother. 53:4533–36
    [Google Scholar]
  106. 106. 
    Majji S, Wijayalath W, Shashikumar S, Brumeanu TD, Casares S. 2018. Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity. Malaria J 17:114
    [Google Scholar]
  107. 107. 
    Schäfer C, Roobsoong W, Kangwanrangsan N, Bardelli M, Rawlinson TA et al. 2020. A humanized mouse model for Plasmodium vivax to test interventions that block liver stage to blood stage transition and blood stage infection. iScience 23:101381
    [Google Scholar]
  108. 108. 
    Douam F, Ziegler CGK, Hrebikova G, Fant B, Leach R et al. 2018. Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses. Nat. Commun. 9:5031
    [Google Scholar]
  109. 109. 
    Ghosn S, Chamat S, Prieur E, Stephan A, Druilhe P, Bouharoun-Tayoun H 2018. Evaluating human immune responses for vaccine development in a novel human spleen cell-engrafted NOD-SCID-IL2rγnull mouse model. Front. Immunol. 9:601
    [Google Scholar]
  110. 110. 
    Cheng L, Zhang Z, Li G, Li F, Wang L et al. 2017. Human innate responses and adjuvant activity of TLR ligands in vivo in mice reconstituted with a human immune system. Vaccine 35:6143–53
    [Google Scholar]
  111. 111. 
    Yao Y, Lai R, Afkhami S, Haddadi S, Zganiacz A et al. 2017. Enhancement of antituberculosis immunity in a humanized model system by a novel virus-vectored respiratory mucosal vaccine. J. Infect. Dis. 216:135–45
    [Google Scholar]
  112. 112. 
    Kametani Y, Shiina M, Katano I, Ito R, Ando K et al. 2006. Development of human–human hybridoma from anti-Her-2 peptide–producing B cells in immunized NOG mouse. Exp. Hematol. 34:1239–47
    [Google Scholar]
  113. 113. 
    Singh M, Singh P, Gaudray G, Musumeci L, Thielen C et al. 2012. An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2RγNULL mice allows HIV replication and development of anti-HIV immune responses. PLOS ONE 7:e38491
    [Google Scholar]
  114. 114. 
    Yi G, Xu X, Abraham S, Petersen S, Guo H et al. 2017. A DNA vaccine protects human immune cells against Zika virus infection in humanized mice. EBioMedicine 25:87–94
    [Google Scholar]
  115. 115. 
    Schmitt K, Charlins P, Veselinovic M, Kinner-Bibeau L, Hu S et al. 2018. Zika viral infection and neutralizing human antibody response in a BLT humanized mouse model. Virology 515:235–42
    [Google Scholar]
  116. 116. 
    Claiborne DT, Dudek TE, Maldini CR, Power KA, Ghebremichael M et al. 2019. Immunization of BLT humanized mice redirects T cell responses to Gag and reduces acute HIV-1 viremia. J. Virol. 93:e00814–19
    [Google Scholar]
  117. 117. 
    Pardi N, Secreto AJ, Shan X, Debonera F, Glover J et al. 2017. Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge. Nat. Commun. 8:14630
    [Google Scholar]
  118. 118. 
    Wahl A, De C, Fernandez MA, Lenarcic EM, Xu Y et al. 2019. Precision mouse models with expanded tropism for human pathogens. Nat. Biotechnol. 37:1163–73
    [Google Scholar]
  119. 119. 
    Lang J, Ota T, Kelly M, Strauch P, Freed BM et al. 2016. Receptor editing and genetic variability in human autoreactive B cells. J. Exp. Med. 213:93–108
    [Google Scholar]
  120. 120. 
    Andrade D, Redecha PB, Vukelic M, Qing X, Perino G et al. 2011. Engraftment of peripheral blood mononuclear cells from systemic lupus erythematosus and antiphospholipid syndrome patient donors into BALB-RAG-2−/−IL-2Rγ−/− mice: a promising model for studying human disease. Arthritis Rheum 63:2764–73
    [Google Scholar]
  121. 121. 
    Mihaylova N, Chipinski P, Bradyanova S, Velikova T, Ivanova-Todorova E et al. 2020. Suppression of autoreactive T and B lymphocytes by anti-annexin A1 antibody in a humanized NSG murine model of systemic lupus erythematosus. Clin. Exp. Immunol. 199:278–93
    [Google Scholar]
  122. 122. 
    Gunawan M, Her Z, Liu M, Tan SY, Chan XY et al. 2017. A novel human systemic lupus erythematosus model in humanised mice. Sci. Rep. 7:16642
    [Google Scholar]
  123. 123. 
    Ishikawa Y, Usui T, Shiomi A, Shimizu M, Murakami K, Mimori T 2014. Functional engraftment of human peripheral T and B cells and sustained production of autoantibodies in NOD/LtSzscid/IL-2Rγ−/− mice. Eur. J. Immunol. 44:113453–63
    [Google Scholar]
  124. 124. 
    Borsotti C, Danzl NM, Nauman G, Hölzl MA, French C et al. 2017. HSC extrinsic sex-related and intrinsic autoimmune disease-related human B-cell variation is recapitulated in humanized mice. Blood Adv 1:2007–18
    [Google Scholar]
  125. 125. 
    Chang N-H, Inman RD, Dick JE, Wither JE 2010. Bone marrow-derived human hematopoietic stem cells engraft NOD/SCID mice and traffic appropriately to an inflammatory stimulus in the joint. J. Rheumatol. 37:496–502
    [Google Scholar]
  126. 126. 
    Misharin AV, Haines GK, Rose S, Gierut AK, Hotchkiss RS, Perlman H. 2012. Development of a new humanized mouse model to study acute inflammatory arthritis. J. Transl. Med. 10:190
    [Google Scholar]
  127. 127. 
    Kuwana Y, Takei M, Yajima M, Imadome K-I, Inomata H et al. 2011. Epstein-Barr virus induces erosive arthritis in humanized mice. PLOS ONE 6:e26630
    [Google Scholar]
  128. 128. 
    Brehm MA, Bortell R, Diiorio P, Leif J, Laning J et al. 2010. Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rγnull Ins2Akita mice. Diabetes 59:2265–70
    [Google Scholar]
  129. 129. 
    Milam AAV, Maher SE, Gibson JA, Lebastchi J, Wen L et al. 2014. A humanized mouse model of autoimmune insulitis. Diabetes 63:1712–24
    [Google Scholar]
  130. 130. 
    Teufel A, Itzel T, Erhart W, Brosch M, Wang XY et al. 2016. Comparison of gene expression patterns between mouse models of nonalcoholic fatty liver disease and liver tissues from patients. Gastroenterology 151:513–25.e0
    [Google Scholar]
  131. 131. 
    Jiang C, Li P, Ruan X, Ma Y, Kawai K et al. 2020. Comparative transcriptomics analyses in livers of mice, humans, and humanized mice define human-specific gene networks. Cells 9:122566
    [Google Scholar]
  132. 132. 
    Ganz M, Szabo G. 2013. Immune and inflammatory pathways in NASH. Hepatol. Int. 7:771–81
    [Google Scholar]
  133. 133. 
    Febbraio MA, Reibe S, Shalapour S, Ooi GJ, Watt MJ, Karin M. 2019. Preclinical models for studying NASH-driven HCC: How useful are they?. Cell Metab 29:18–26
    [Google Scholar]
  134. 134. 
    Minniti ME, Pedrelli M, Vedin L-L, Delbès A-S, Denis RGP et al. 2020. Insights from liver-humanized mice on cholesterol lipoprotein metabolism and LXR-agonist pharmacodynamics in humans. Hepatology 72:656–70
    [Google Scholar]
  135. 135. 
    Her Z, Tan JHL, Lim Y-S, Tan SY, Chan XY et al. 2020. CD4+ T cells mediate the development of liver fibrosis in high fat diet-induced NAFLD in humanized mice. Front. Immunol. 11:580968
    [Google Scholar]
  136. 136. 
    Dibner C, Schibler U. 2015. Circadian timing of metabolism in animal models and humans. J. Intern. Med. 277:513–27
    [Google Scholar]
  137. 137. 
    Zhao Y, Liu M, Chan XY, Tan SY, Subramaniam S et al. 2017. Uncovering the mystery of opposite circadian rhythms between mouse and human leukocytes in humanized mice. Blood J. Am. Soc. Hematol. 130:1995–2005
    [Google Scholar]
  138. 138. 
    Brenner DA. 2018. Of mice and men and nonalcoholic steatohepatitis. Hepatology 68:2059–61
    [Google Scholar]
  139. 139. 
    Wilkinson AC, Ishida R, Kikuchi M, Sudo K, Morita M et al. 2019. Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature 571:117–21
    [Google Scholar]
  140. 140. 
    Taoka K, Arai S, Kataoka K, Hosoi M, Miyauchi M et al. 2018. Using patient-derived iPSCs to develop humanized mouse models for chronic myelomonocytic leukemia and therapeutic drug identification, including liposomal clodronate. Sci. Rep. 8:15855
    [Google Scholar]
  141. 141. 
    Chen Q. 2017. The niche for hematopoietic stem cell expansion: a collaboration network. Cell. Mol. Immunol. 14:865–67
    [Google Scholar]
  142. 142. 
    Volk V, Reppas AI, Robert PA, Spineli LM, Sundarasetty BS et al. 2017. Multidimensional analysis integrating human T-cell signatures in lymphatic tissues with sex of humanized mice for prediction of responses after dendritic cell immunization. Front. Immunol. 8:1709
    [Google Scholar]
  143. 143. 
    Denton PW, Nochi T, Lim A, Krisko JF, Martinez-Torres F et al. 2012. IL-2 receptor γ-chain molecule is critical for intestinal T-cell reconstitution in humanized mice. Mucosal Immunol 5:555–66
    [Google Scholar]
  144. 144. 
    Allam A, Majji S, Peachman K, Jagodzinski L, Kim J et al. 2015. TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1. Sci. Rep. 5:10443
    [Google Scholar]
  145. 145. 
    Tarrant JC, Binder ZA, Bugatti M, Vermi W, van den Oord J et al. 2021. Pathology of macrophage activation syndrome in humanized NSGS mice. Res. Veterinary Sci. 134:137–46
    [Google Scholar]
  146. 146. 
    Mencarelli A, Gunawan M, Yong KSM, Bist P, Tan WWS et al. 2020. A humanized mouse model to study mast cells mediated cutaneous adverse drug reactions. J. Leukoc. Biol. 107:797–807
    [Google Scholar]
  147. 147. 
    Pujhari S, Rasgon JL. 2020. Mice with humanized-lungs and immune system—an idealized model for COVID-19 and other respiratory illness. Virulence 11:486–88
    [Google Scholar]
  148. 148. 
    Bao L, Deng W, Huang B, Gao H, Liu J et al. 2020. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature 583:830–33
    [Google Scholar]
  149. 149. 
    Mori M, Furuhashi K, Danielsson JA, Hirata Y, Kakiuchi M et al. 2019. Generation of functional lungs via conditional blastocyst complementation using pluripotent stem cells. Nat. Med. 25:1691–98
    [Google Scholar]
  150. 150. 
    Stripecke R, Münz C, Schuringa JJ, Bissig KD, Soper B et al. 2020. Innovations, challenges, and minimal information for standardization of humanized mice. EMBO Mol. Med. 12:e8662
    [Google Scholar]
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