Establishing Humanized Mice Using Stem Cells: Maximizing the Potential

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2008 Apr 26

PMID 18435804

Citations 15

Authors

D Bernard

M Peakman

A C Hayday

Affiliations

Soon will be listed here.

Abstract

Studies on physiology and pathology as they relate to the immune system draw heavily upon rodent models. With the increasing impetus provided by initiatives in translational medicine, the demand for ever more sophisticated, 'humanized' murine models is greater than ever. However, the design and implementation of studies in such mice is far from trivial. Here we provide a technical perspective on the increasing interest in developing humanized mice. We give examples of primary data starting with the routine procurement of human donor material, through CD34(+) cell purification prior to engraftment to injection into immunocompromised mice. Our goal is to provide practical advice to the many investigators who may be commencing or considering such studies.

Citing Articles

Humanized Mice as a Model to Assess the Response of Human Hematopoietic Stem Cells to Irradiation.

Atamanyuk N, Andreev S, Peretykin A, Styazhkina E, Obvintseva N, Tryapitsina G Bull Exp Biol Med. 2023; 176(1):34-37.

PMID: 38091132 DOI: 10.1007/s10517-023-05962-4.

Patient-derived precision cut tissue slices from primary liver cancer as a potential platform for preclinical drug testing.

Jagatia R, Doornebal E, Rastovic U, Harris N, Feyide M, Lyons A EBioMedicine. 2023; 97:104826.

PMID: 37806285 PMC: 10667128. DOI: 10.1016/j.ebiom.2023.104826.

Humanized Mouse Model of HIV Infection.

Leontyev D, Glazkova D, Bezborodova O, Tsyganova G, Urusov F, Pankratov A Bull Exp Biol Med. 2023; 175(1):63-66.

PMID: 37338766 DOI: 10.1007/s10517-023-05812-3.

Advances in Research of Adult Gliomas.

Finch A, Solomou G, Wykes V, Pohl U, Bardella C, Watts C Int J Mol Sci. 2021; 22(2).

PMID: 33477674 PMC: 7831916. DOI: 10.3390/ijms22020924.

An Improved Patient-Derived Xenograft Humanized Mouse Model for Evaluation of Lung Cancer Immune Responses.

Meraz I, Majidi M, Meng F, Shao R, Ha M, Neri S Cancer Immunol Res. 2019; 7(8):1267-1279.

PMID: 31186248 PMC: 7213862. DOI: 10.1158/2326-6066.CIR-18-0874.

References

Maerten P, Kwon B, Shen C, De Hertogh G, Cadot P, Bullens D . Involvement of 4-1BB (CD137)-4-1BBligand interaction in the modulation of CD4 T cell-mediated inflammatory colitis. Clin Exp Immunol. 2006; 143(2):228-36. PMC: 1809580. DOI: 10.1111/j.1365-2249.2005.02991.x. View

DiSanto J, Muller W, Fischer A, Rajewsky K . Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. Proc Natl Acad Sci U S A. 1995; 92(2):377-81. PMC: 42743. DOI: 10.1073/pnas.92.2.377. View

Greiner D, Hesselton R, Shultz L . SCID mouse models of human stem cell engraftment. Stem Cells. 1998; 16(3):166-77. DOI: 10.1002/stem.160166. View

Vassilev T, Mihaylova N, Voynova E, Nikolova M, Kazatchkine M, Kaveri S . IgM-enriched human intravenous immunoglobulin suppresses T lymphocyte functions in vitro and delays the activation of T lymphocytes in hu-SCID mice. Clin Exp Immunol. 2006; 145(1):108-15. PMC: 1942011. DOI: 10.1111/j.1365-2249.2006.03098.x. View

Takenaka K, Prasolava T, Wang J, Mortin-Toth S, Khalouei S, Gan O . Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nat Immunol. 2007; 8(12):1313-23. DOI: 10.1038/ni1527. View

Sun Z, Denton P, Estes J, Othieno F, Wei B, Wege A . Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1. J Exp Med. 2007; 204(4):705-14. PMC: 2118553. DOI: 10.1084/jem.20062411. View

Islas-Ohlmayer M, Padgett-Thomas A, Domiati-Saad R, Melkus M, Cravens P, Martin M . Experimental infection of NOD/SCID mice reconstituted with human CD34+ cells with Epstein-Barr virus. J Virol. 2004; 78(24):13891-900. PMC: 533956. DOI: 10.1128/JVI.78.24.13891-13900.2004. View

Bonnet D, Bhatia M, Wang J, Kapp U, Dick J . Cytokine treatment or accessory cells are required to initiate engraftment of purified primitive human hematopoietic cells transplanted at limiting doses into NOD/SCID mice. Bone Marrow Transplant. 1999; 23(3):203-9. DOI: 10.1038/sj.bmt.1701564. View

Bente D, Melkus M, Garcia J, Rico-Hesse R . Dengue fever in humanized NOD/SCID mice. J Virol. 2005; 79(21):13797-9. PMC: 1262615. DOI: 10.1128/JVI.79.21.13797-13799.2005. View

10.

Melkus M, Estes J, Padgett-Thomas A, Gatlin J, Denton P, Othieno F . Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nat Med. 2006; 12(11):1316-22. DOI: 10.1038/nm1431. View

11.

Bhatia M, Wang J, Kapp U, Bonnet D, Dick J . Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci U S A. 1997; 94(10):5320-5. PMC: 24676. DOI: 10.1073/pnas.94.10.5320. View

12.

Mosier D, Gulizia R, Baird S, Wilson D . Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature. 1988; 335(6187):256-9. DOI: 10.1038/335256a0. View

13.

Lowry P, Shultz L, Greiner D, Hesselton R, Kittler E, Tiarks C . Improved engraftment of human cord blood stem cells in NOD/LtSz-scid/scid mice after irradiation or multiple-day injections into unirradiated recipients. Biol Blood Marrow Transplant. 1996; 2(1):15-23. View

14.

Ueda T, Yoshida M, Yoshino H, Kobayashi K, Kawahata M, Ebihara Y . Hematopoietic capability of CD34+ cord blood cells: a comparison with CD34+ adult bone marrow cells. Int J Hematol. 2001; 73(4):457-462. DOI: 10.1007/BF02994007. View

15.

Serreze D, Chen Y . Of mice and men: use of animal models to identify possible interventions for the prevention of autoimmune type 1 diabetes in humans. Trends Immunol. 2005; 26(11):603-7. DOI: 10.1016/j.it.2005.08.012. View

16.

Kuci S, Wessels J, Buhring H, Schilbach K, Schumm M, Seitz G . Identification of a novel class of human adherent CD34- stem cells that give rise to SCID-repopulating cells. Blood. 2002; 101(3):869-76. DOI: 10.1182/blood-2002-03-0711. View

17.

Sugamura K, Asao H, Kondo M, Tanaka N, Ishii N, Ohbo K . The interleukin-2 receptor gamma chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu Rev Immunol. 1996; 14:179-205. DOI: 10.1146/annurev.immunol.14.1.179. View

18.

Christianson S, Greiner D, Schweitzer I, Gott B, Beamer G, Schweitzer P . Role of natural killer cells on engraftment of human lymphoid cells and on metastasis of human T-lymphoblastoid leukemia cells in C57BL/6J-scid mice and in C57BL/6J-scid bg mice. Cell Immunol. 1996; 171(2):186-99. DOI: 10.1006/cimm.1996.0193. View

19.

Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti J, Lanzavecchia A . Development of a human adaptive immune system in cord blood cell-transplanted mice. Science. 2004; 304(5667):104-7. DOI: 10.1126/science.1093933. View

20.

Shultz L, Lyons B, Burzenski L, Gott B, Chen X, Chaleff S . Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005; 174(10):6477-89. DOI: 10.4049/jimmunol.174.10.6477. View