Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Engraftment

Stem cell factor improves SCID-repopulating activity of human umbilical cord blood-derived hematopoietic stem/progenitor cells in xenotransplanted NOD/SCID mouse model

Bone Marrow Transplantation volume 35, pages 137–142 (2005)Cite this article

Abstract

Summary:

Poor in vivo homing capacity of hematopoietic stem/progenitor cells (HS/PCs) from umbilical cord blood (UCB) can be reversed by short-term ex vivo manipulation with recombinant human stem cell factor (rHuSCF). This study was designed to evaluate the effect of ex vivo manipulation of UCB-derived HS/PCs with rHuSCF on human cell engraftment rates in xenotransplanted NOD/SCID mouse model. The human cell engraftment rates in xenotransplanted primary and secondary NOD/SCID mice were characterized using four-color flow cytometric analysis and progenitor assay. Grafts of rHuSCF-treated UCB CD34+ cells resulted in significantly higher levels of human cell engraftment than that of nontreated ones in both xenotransplanted primary and secondary NOD/SCID recipients. Fresh UCB CD34+ cells did not express either of the matrix metalloproteinase (MMP) family members MMP-2 or MMP-9. rHuSCF-treated UCB CD34+ cells expressed significant levels of MMP-2 and MMP-9. Pretreatment of UCB CD34+ cells with the specific MMP inhibitor completely blocked human cell engraftment in xenotransplanted NOD/SCID recipients. Our results indicate that ex vivo manipulation of human HS/PCs with rHuSCF might provide an optimal approach to develop more effective stem cell-based therapies in situations where engraftment is delayed due to limiting HS/PCs number, for example, UCB transplantation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Gluckman E, Rocha V, Boyer-Chammard A et al. Outcome of cord-blood transplantation from related and unrelated donors. N Engl J Med 1997; 337: 373–381.

    Article  CAS  PubMed  Google Scholar 

  2. Rubinstein P, Carrier C, Scaradavou A et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 1998; 339: 1565–1577.

    Article  CAS  PubMed  Google Scholar 

  3. Gluckman E . Current status of umbilical cord blood hematopoietic stem cell transplantation. Exp Hematol 2000; 28: 1197–1205.

    Article  CAS  PubMed  Google Scholar 

  4. Laughlin MJ . Umbilical cord blood for allogeneic transplantation in children and adults. Bone Marrow Transplant 2001; 27: 1–6.

    Article  CAS  PubMed  Google Scholar 

  5. Gluckman E, Broxmeyer HA, Auerbach AD et al. Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med 1989; 321: 1174–1178.

    Article  CAS  PubMed  Google Scholar 

  6. Wagner JE, Barker JN, DeFor TE et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 2002; 100: 1611–1618.

    CAS  PubMed  Google Scholar 

  7. Dorrel C, Gan OI, Pereira DS et al. Expansion of human cord blood CD34+CD38− cells in ex vivo culture during retroviral transduction without a corresponding increase in SCID repopulating cell (SRC) frequency: dissociation of SRC phenotype and function. Blood 2000; 95: 102–110.

    Google Scholar 

  8. Xu R, Reems JA . Umbilical cord blood progeny cells that retain a CD34+ phenotype after ex vivo expansion have less engraftment potential than unexpanded CD34+ cells. Transfusion 2001; 41: 213–218.

    Article  CAS  PubMed  Google Scholar 

  9. Bark JN, Weisdorf DJ, DeFor TE et al. Multiple unit unrelated donor umbilical cord blood transplantation in high risk adults with hematologic malignancies: impact on engraftment and chimerism (abstract). Blood 2002; 100 (Suppl 1): 41a.

    Google Scholar 

  10. Vormoor J, Lapidot T, Pflumio F et al. Immature human cord blood progenitors engraft and proliferate to high levels in severe combined immunodeficient mice. Blood 1994; 83: 2489–2497.

    CAS  PubMed  Google Scholar 

  11. Ballen KK, Valinski H, Greiner D et al. Variables to predict engraftment of umbilical cord blood into immunodeficient mice: usefulness of the non-obese diabetic-severe combined immunodeficient assay. Br J Haematol 2001; 114: 211–218.

    Article  CAS  PubMed  Google Scholar 

  12. Hogan CJ, Shpall EJ, McNulty O et al. Engraftment and development of human CD34+-enriched cells from umbilical cord blood in NOD/LtSz-scid/scid mice. Blood 1997; 90: 85–96.

    CAS  PubMed  Google Scholar 

  13. Cashman JD, Lapidot T, Wang JC et al. Kinetic evidence of the regeneration of multilineage hematopoiesis from primitive cells in normal human bone marrow transplanted into immunodeficient mice. Blood 1997; 89: 4307–4316.

    CAS  PubMed  Google Scholar 

  14. Perez LE, Rinder HM, Wang C et al. Xenotransplantation of immunodeficient mice with mobilized human blood CD34+ cells provides an in vivo model for human megakaryocytopoiesis and platelet production. Blood 2001; 97: 1635–1643.

    Article  CAS  PubMed  Google Scholar 

  15. Voermans C, Kooi ML, Rodenhuis S et al. In vitro migratory capacity of CD34+ cells is related to hematopoietic recovery after autologous stem cell transplantation. Blood 2001; 97: 799–804.

    Article  CAS  PubMed  Google Scholar 

  16. van Hennik PB, de Koning AE, Ploemacher RE . Seeding efficiency of primitive human hematopoietic cells in nonobese diabetic/severe combined immune deficiency mice: implications for stem cell frequency assessment. Blood 1999; 94: 3055–3061.

    CAS  PubMed  Google Scholar 

  17. Cashman JD, Eaves CJ . High marrow seeding efficiency of human lymphomyeloid repopulating cells in irradiated NOD/SCID mice. Blood 2000; 96: 3979–3981.

    CAS  PubMed  Google Scholar 

  18. Zheng Y, Watanabe N, Nagamura-Inoue T et al. Ex vivo manipulation of umbilical cord blood-derived hematopoietic stem/progenitor cells with recombinant human stem cell factor can up-regulate levels of homing-essential molecules to increase their transmigratory potential. Exp Hematol 2003; 31: 1237–1246.

    Article  CAS  PubMed  Google Scholar 

  19. Srour EF, Jetmore A, Wolber FW et al. Homing, cell cycle kinetics and fate of transplanted hematopoietic stem cells. Leukemia 2001; 15: 1681–1684.

    Article  CAS  PubMed  Google Scholar 

  20. Jetmore A, Plett PA, Tong X et al. Homing efficiency, cell cycle kinetics, and survival of quiescent and cycling human CD34+ cells transplanted into conditioned NOD/SCID recipients. Blood 2001; 99: 1585–1593.

    Article  Google Scholar 

  21. Peled A, Petit I, Kollet O et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 1999; 283: 845–848.

    Article  CAS  PubMed  Google Scholar 

  22. Kollet O, Spiegel A, Peled A et al. Rapid and efficient homing of human CD34+CD38−/lowCXCR4+ stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2m(null) mice. Blood 2001; 97: 3283–3291.

    Article  CAS  PubMed  Google Scholar 

  23. Hart C, Drewel D, Mueller G et al. Expression and function of homing-essential molecules and enhanced in vivo homing ability of human peripheral blood-derived hematopoietic progenitor cells after stimulation with stem cell factor. Stem Cells 2004; 22: 580–589.

    Article  CAS  PubMed  Google Scholar 

  24. Nagase H, Woessner Jr JF . Matrix metalloproteinases. J Biol Chem 1999; 274: 21491–21494.

    Article  CAS  PubMed  Google Scholar 

  25. Janowska-Wieczorek A, Marquez LA, Nabholtz JM et al. Growth factors and cytokines upregulate gelatinase expression in bone marrow CD34+ cells and their transmigration through reconstituted basement membrane. Blood 1999; 93: 3379–3390.

    CAS  PubMed  Google Scholar 

  26. Lane WJ, Dias S, Hattori K et al. Stromal-derived factor 1-induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases. Blood 2000; 96: 4152–4159.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China

    Y Zheng, A Sun & Z C Han

Authors
  1. Y Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Z C Han
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z C Han.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zheng, Y., Sun, A. & Han, Z. Stem cell factor improves SCID-repopulating activity of human umbilical cord blood-derived hematopoietic stem/progenitor cells in xenotransplanted NOD/SCID mouse model. Bone Marrow Transplant 35, 137–142 (2005). https://doi.org/10.1038/sj.bmt.1704751

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704751

Keywords

This article is cited by

Search

Advanced search

Quick links