Immunodeficient Mouse Models to Study Human Stem Cell-Mediated Tissue Repair

  • Ping Zhou
  • Sarah Hohm
  • Ben Capoccia
  • Louisa Wirthlin
  • David Hess
  • Dan Link
  • Jan Nolta
Part of the Methods in Molecular Biology™ book series (MIMB, volume 430)

Summary

Hematopoietic stem cell transplantation has traditionally been used to reconstitute blood cell lineages that had formed abnormally because of genetic mutations, or that had been eradicated to treat a disease such as leukemia. However, in recent years, much attention has been paid to the new concept of “stem cell plasticity,” and the hope that stem cells could be used to repair damaged tissues generated immense excitement. The field is now in a more realistic and critical period of intense investigation and the concept of cell fusion to explain some of the observed effects has been shown after specific types of damage in liver and muscle, both organs that contain a high number of multinucleate cells. The field is still an extremely exciting one, and many questions remain to be answered before stem cell therapy for tissue repair can be used effectively in the clinic. Immune deficient mouse models of tissue damage provide a system in which human stem cell migration to sites of damage and subsequent contribution to repair can be carefully evaluated. This chapter gives detailed instructions for methods to study human stem cell contribution to damaged liver and to promote repair of damaged vasculature in immune deficient mouse models.

Key Words

Human stem cells immune deficient mice tissue repair revascularization liver 

References

  1. 1.
    Caplan, A. I. &; Dennis, J. E. (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98, 1076–1084.CrossRefPubMedGoogle Scholar
  2. 2.
    Schatteman, G. C. (2004) Non-classical mechanisms of heart repair. Mol Cell Biochem 264, 103–117.CrossRefPubMedGoogle Scholar
  3. 3.
    Yoshioka, T., Ageyama, N., Shibata, H., Yasu, T., Misawa, Y., Takeuchi, K., Matsui, K., Yamamoto, K., Terao, K., Shimada, K., Ikeda, U., Ozawa, K. & Hanazono, Y. (2005) Repair of infarcted myocardium mediated by transplanted bone marrow-derived CD34+ stem cells in a nonhuman primate model. Stem Cells 23, 355–364.CrossRefPubMedGoogle Scholar
  4. 4.
    Goodell, M. A., Brose, K., Paradis, G., Conner, A. S. &; Mulligan, R. C. (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183, 1797–1806.CrossRefPubMedGoogle Scholar
  5. 5.
    Goodell, M. A., Rosenzweig, M., Kim, H., Marks, D. F., DeMaria, M., Paradis, G., Grupp, S. A., Sieff, C. A., Mulligan, R. C. & Johnson, R. P. (1997) Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med 3, 1337–1345.CrossRefPubMedGoogle Scholar
  6. 6.
    Bhatia, M., Bonnet, D., Murdoch, B., Gan, O. I. & Dick, J. E. (1998) A newly discovered class of human hematopoietic cells with SCID- repopulating activity [see comments]. Nat Med 4, 1038–1045.CrossRefPubMedGoogle Scholar
  7. 7.
    Dao, M. A., Arevalo, J. & Nolta, J. A. (2003) Reversibility of CD34 expression on human hematopoietic stem cells that retain the capacity for secondary reconstitution. Blood 101, 112–118.CrossRefPubMedGoogle Scholar
  8. 8.
    Dao, M. A. & Nolta, J. A. (2000) CD34: to select or not to select? That is the question. Leukemia 14, 773–776.CrossRefPubMedGoogle Scholar
  9. 9.
    Hess, D. A., Karanu, F. N., Levac, K., Gallacher, L. & Bhatia, M. (2003) Coculture and transplant of purified CD34(+)Lin(-) and CD34(-)Lin(-) cells reveals functional interaction between repopulating hematopoietic stem cells. Leukemia 17, 1613–1625.CrossRefPubMedGoogle Scholar
  10. 10.
    Sato, T., Laver, J. H. & Ogawa, M. (1999) Reversible expression of CD34 by murine hematopoietic stem cells. Blood 94, 2548–2554.PubMedGoogle Scholar
  11. 11.
    Zanjani, E. D., Almeida-Porada, G., Livingston, A. G., Porada, C. D. & Ogawa, M. (1999) Engraftment and multilineage expression of human bone marrow CD34- cells in vivo. Ann N Y Acad Sci 872, 220–231; discussion 231–232.CrossRefPubMedGoogle Scholar
  12. 12.
    Storms, R. W., Goodell, M. A., Fisher, A., Mulligan, R. C. & Smith, C. (2000) Hoechst dye efflux reveals a novel CD7(+)CD34(-) lymphoid progenitor in human umbilical cord blood. Blood 96, 2125–2133.PubMedGoogle Scholar
  13. 13.
    Cai, J., Weiss, M. L. & Rao, M. S. (2004) In search of “stemness”. Exp Hematol 32, 585–598.CrossRefPubMedGoogle Scholar
  14. 14.
    Fallon, P., Gentry, T., Balber, A. E., Boulware, D., Janssen, W. E., Smilee, R., Storms, R. W. & Smith, C. (2003) Mobilized peripheral blood SSCloALDHbr cells have the phenotypic and functional properties of primitive haematopoietic cells and their number correlates with engraftment following autologous transplantation. Br J Haematol 122, 99–108.CrossRefPubMedGoogle Scholar
  15. 15.
    Hess, D. A., Meyerrose, T. E., Wirthlin, L., Craft, T. P., Herrbrich, P. E., Creer, M. H. & Nolta, J. A. (2004) Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity. Blood 104, 1648–1655.CrossRefPubMedGoogle Scholar
  16. 16.
    Takebe, N., Zhao, S. C., Adhikari, D., Mineishi, S., Sadelain, M., Hilton, J., Colvin, M., Banerjee, D. & Bertino, J. R. (2001) Generation of dual resistance to 4-hydroperoxycyclophosphamide and methotrexate by retroviral transfer of the human aldehyde dehydrogenase class 1 gene and a mutated dihydrofolate reductase gene. Mol Ther 3, 88–96.CrossRefPubMedGoogle Scholar
  17. 17.
    Jones, R. J., Barber, J. P., Vala, M. S., Collector, M. I., Kaufmann, S. H., Ludeman, S. M., Colvin, O. M. & Hilton, J. (1995) Assessment of aldehyde dehydrogenase in viable cells. Blood 85, 2742–2746.PubMedGoogle Scholar
  18. 18.
    Jones, R. J., Collector, M. I., Barber, J. P., Vala, M. S., Fackler, M. J., May, W. S., Griffin, C. A., Hawkins, A. L., Zehnbauer, B. A., Hilton, J., Colvin, O. M. & Sharkis, S. J. (1996) Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. Blood 88, 487–491.PubMedGoogle Scholar
  19. 19.
    Meyerrose, T. E., Herrbrich, P., Hess, D. A. & Nolta, J. A. (2003) Immune-deficient mouse models for analysis of human stem cells. Biotechniques 35, 1262–1272.PubMedGoogle Scholar
  20. 20.
    Glimm, H., Eisterer, W., Lee, K., Cashman, J., Holyoake, T. L., Nicolini, F., Shultz, L. D., von Kalle, C. & Eaves, C. J. (2001) Previously undetected human hematopoietic cell populations with short-term repopulating activity selectively engraft NOD/SCID-beta2 microglobulin-null mice. J Clin Invest 107, 199–206.CrossRefPubMedGoogle Scholar
  21. 21.
    Christianson, S. W., Greiner, D. L., Hesselton, R. A., Leif, J. H., Wagar, E. J., Schweitzer, I. B., Rajan, T. V., Gott, B., Roopenian, D. C. & Shultz, L. D. (1997) Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice. J Immunol 158, 3578–3586.PubMedGoogle Scholar
  22. 22.
    Hofling, A. A., Vogler, C., Creer, M. H. & Sands, M. S. (2003) Engraftment of human CD34+ cells leads to widespread distribution of donor-derived cells and correction of tissue pathology in a novel murine xenotransplantation model of lysosomal storage disease. Blood 101, 2054–2063.CrossRefPubMedGoogle Scholar
  23. 23.
    Meyerrose, T. E., De Ugarte, D. A., Hofling, A. A., Herrbrich, P. E., Cordonnier, T. D., Shultz, L. D., Eagon, J. C., Wirthlin, L., Sands, M. S., Hedrick, M. A. & Nolta, J. A. (2006) In vivo distribution of human adipose-derived MSC. Stem Cells 25, 220–227.CrossRefPubMedGoogle Scholar
  24. 24.
    Wang, X., Ge, S., McNamara, G., Hao, Q. L., Crooks, G. M. & Nolta, J. A. (2003) Albumin expressing hepatocyte-like cells develop in the livers of immune-deficient mice transmitted with highly purified human hematopoietic stem cells. Blood, 101, 4201–4208.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Ping Zhou
    • 1
  • Sarah Hohm
    • 1
  • Ben Capoccia
    • 1
  • Louisa Wirthlin
    • 1
  • David Hess
    • 1
  • Dan Link
    • 1
  • Jan Nolta
    • 1
  1. 1.Department of Internal Medicine, Division of Oncology,Hematopoietic Development and Malignancy GroupWashington University School of MedicineSt. Louis

Personalised recommendations