Skip to main content

Advertisement

SpringerLink
Log in

Effect of mesenchymal stem cell transplantation on the engraftment of human hematopoietic stem cells and leukemic cells in mice model

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

We investigated the effect of human bone marrow-derived mesenchymal stem cells on engraftment of human umbilical cord blood CD34+ cells and acute myelogenous leukemia cells and also assessed the homing capability of MSCs. Forty-two NOD/SCID mice were administered sublethal irradiation followed by various cell doses of intravenous UCB CD34+ cells with or without MSCs. Another 12 NOD/SCID mice were also sublethally irradiated followed by intravenous injection of AML cells with or without MSCs. In ten of these mice, MSCs were genetically modified with an adenoviral vector encoding eGFP gene for tracking purpose. Cotransplantation of UCB CD34+ cells and MSCs resulted in a significant increase in bone marrow engraftment after 6 weeks, and the engraftment promoting effect of MSCs was proportional to the dose of MSCs and obvious when low doses of UCB CD34+ cells were given. There was no effect of MSCs on AML cells engraftment. All of the ten mice transplanted with eGFP-transfected MSCs showed positive for eGFP in their major organs. These data demonstrate that MSCs promote engraftment of UCB CD34+cells in bone marrow, but exert no effect on engraftment of AML cells, and are capable of homing to the major organs including bone marrow following intravenous infusion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Torok-Storb B, Holmberg L. Role of marrow microenvironment in engraftment and maintenance of allogeneic hematopoietic stem cells. Bone Marrow Transplant. 1994;14(suppl. 4):S71–3.

    PubMed  Google Scholar 

  2. Uchida N, Fleming WH, Alpern EJ, Weissman IL. Heterogeneity of hematopoietic stem cells. Curr Opin Immunol. 1993;5:177–84.

    Article  PubMed  CAS  Google Scholar 

  3. Nilsson SK, Johnston HM, Coverdale JA. Spatial localization of transplanted hemopoietic stem cells: inferences for the localization of stem cell niches. Blood. 2001;97:2293–9.

    Article  PubMed  CAS  Google Scholar 

  4. Schwartz GN, Warren MK, Rothwell SW, et al. Post-chemotherapy and cytokine pretreated marrow stromal cell layers suppress hematopoiesis from normal donor CD34+ cells. Bone Marrow Transplant. 1998;22:457–68.

    Article  PubMed  CAS  Google Scholar 

  5. Roingeard F, Binet C, Lecron JC, Truglio D, Colombat P, Domenech J. Cytokines released in vitro by stromal cells from autologous bone marrow transplant patients with lymphoid malignancy. Eur J Haematol. 1998;61:100–8.

    Article  PubMed  CAS  Google Scholar 

  6. O’Flaherty E, Sparrow R, Szer J. Bone marrow stromal function from patients after bone marrow transplantation. Bone Marrow Transplant. 1995;15:207–12.

    PubMed  CAS  Google Scholar 

  7. Galotto M, Berisso G, Delfino L, et al. Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients. Exp Hematol. 1999;27:1460–6.

    Article  PubMed  CAS  Google Scholar 

  8. Devine SM, Bartholomew AM, Mahmud N, et al. Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion. Exp Hematol. 2001;29:244–55.

    Article  PubMed  CAS  Google Scholar 

  9. Nilsson SK, Dooner MS, Weier HU, et al. Cells capable of bone production engraft from whole bone marrow transplants in nonablated mice. J Exp Med. 1999;189:729–34.

    Article  PubMed  CAS  Google Scholar 

  10. Almeida-Porada G, Porada CD, Tran N, Zanjani ED. Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation. Blood. 2000;95:3620–7.

    PubMed  CAS  Google Scholar 

  11. Nolta JA, Hanley MB, Kohn DB. Sustained human hematopoiesis in immunodeficient mice by cotransplantation of marrow stroma expressing human interleukin-3: analysis of gene transduction of long-lived progenitors. Blood. 1994;83:3041–51.

    PubMed  CAS  Google Scholar 

  12. Nolta JA, Thiemann FT, Arakawa-Hoyt J, et al. The AFT024 stromal cell line supports long-term ex vivo maintenance of engrafting multipotent human hematopoietic progenitors. Leukemia. 2002;16:352–61.

    Article  PubMed  CAS  Google Scholar 

  13. Brouard N, Chapel A, Neildez-Nguyen TM, et al. Transplantation of stromal cells transduced with the human IL3 gene to stimulate hematopoiesis in human fetal bone grafts in non-obese diabeticsevere combined immunodeficiency mice. Leukemia. 1998;12:1128–35.

    Article  PubMed  CAS  Google Scholar 

  14. Noort WA, Kruisselbrink AB, in’t Anker PS, et al. Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34+ cells in NOD/SCID mice. Exp Hematol. 2002;30:870–8.

    Article  PubMed  Google Scholar 

  15. Koc ON, Gerson SL, Cooper BW, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high dose chemotherapy. J Clin Oncol. 2000;18:307–16.

    PubMed  CAS  Google Scholar 

  16. Koc ON, Peters C, Aubourg P, et al. Bone marrow-derived mesenchymal stem cells remain host-derived despite successful hematopoietic engraftment after allogeneic transplantation in patients with lysosomal and peroxisomal storage diseases. Exp Hematol. 1999;27:1675–81.

    Article  PubMed  CAS  Google Scholar 

  17. Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002;30:42–8.

    Article  PubMed  Google Scholar 

  18. Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99:3838–43.

    Article  PubMed  CAS  Google Scholar 

  19. Lee ST, Jang JH, Cheong JW, et al. Treatment of high risk acute myelogenous leukaemia by myeloablative chemoradiotherapy followed by coinfusion of T-cell depleted haematopoietic stem cells and culture-expanded marrow mesenchymal stem cells from a related donor with one fully mismatched HLA haplotype. Br J Haematol. 2002;118:1128–31.

    Article  PubMed  Google Scholar 

  20. Ringde´n O, Uzunel M, Rasmusson I, et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation. 2006;81:1390–7.

    Article  Google Scholar 

  21. Horwitz EM, Gordon PL, Koo WK, et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc Natl Acad Sci USA. 2002;99:8932–7.

    Article  PubMed  CAS  Google Scholar 

  22. Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC. Green fluorescent protein as a marker for gene expression. Science. 1994;263:802–5.

    Article  PubMed  CAS  Google Scholar 

  23. Doran SE, Ren XD, Betz AL, et al. Gene expression from recombinant viral vectors in the central nervous system after blood–brain barrier disruption. Neurosurgery. 1995;36:965–70.

    Article  PubMed  CAS  Google Scholar 

  24. Walter I, Fleischmann M, Klein D, et al. Rapid and sensitive detection of enhanced green fluorescent protein expression in paraffin sections by confocal laser scanning microscopy. Histochem J. 2000;32:99–103.

    Article  PubMed  CAS  Google Scholar 

  25. Anklesaria P, Kase K, Glowacki J, et al. Engraftment of a clonal bone marrow stromal cell line in vivo stimulates hematopoietic recovery from total body irradiation. Proc Natl Acad Sci USA. 1987;84:7681–5.

    Article  PubMed  CAS  Google Scholar 

  26. Maitra B, Szekely E, Gjini K, et al. Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation. Bone Marrow Transplant. 2004;33:597–604.

    Article  PubMed  CAS  Google Scholar 

  27. Angelopoulou M, Novelli E, Grove JE. Cotransplantation of human mesenchymal stem cells enhances human myelopoiesis and megakaryocytopoiesis in NOD/SCID mice. Exp Hematol. 2003;31:413–20.

    Article  PubMed  CAS  Google Scholar 

  28. Scholzel C, Lowenberg B. Stimulation of proliferation and differentiation of acute myeloid leukemia cells on a bone marrow stroma in culture. Exp Hematol.1985;13:664–9.

    PubMed  CAS  Google Scholar 

  29. Garrido SM, Appelbaum FR, Willman CL, Banker DE. Acute myeloid leukemia cells are protected from spontaneous and drug-induced apoptosis by direct contact with a human bone marrow stromal cell line (HS-5). Exp Hematol. 2001;29:448–57.

    Article  PubMed  CAS  Google Scholar 

  30. Klyushnenkova E, Shustova V, Mosca J, Moseley A. McIntosh KR. Human mesenchymal stem cells induce unresponsiveness in preactivated but not naive alloantigen specific T cells (abstract). Exp Hematol. 1999;27:122.

    Google Scholar 

  31. Devine SM, Cobbs C, Jennings M, Bartholomew A, Hoffman R. Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood. 2003;101:2999–3001.

    Article  PubMed  CAS  Google Scholar 

  32. François S, Bensidhoum M, Mouiseddine M, et al. Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage. Stem Cells. 2006;24:1020–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Ms. Sun Hye Nam and Mr. Hyung Kwan Kim for their technical help in animal experiment and Mr. Jong Ho Ryu for assistance with cell culture.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-ku Shinchon-dong 134, Seoul, 120-752, South Korea

    Seung-Tae Lee

  2. Department of Internal Medicine, National Health Insurance Cooperation Ilsan Hospital, Goyang, Gyeonggi-Do, South Korea

    Hoyoung Maeng

  3. Departments of Microbiology, Pochon Cha University College of Medicine, Seongnam, Gyeonggi-Do, South Korea

    Yong-Joon Chwae

  4. Department of Bioscience and Biotechnology, Sejong University, Seoul, South Korea

    Duk Jae Oh

  5. Department of Obstetrics and Gynecology, Ulsan University College of Medicine, Seoul, South Korea

    Yong-Man Kim

  6. Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea

    Woo Ick Yang

Authors
  1. Seung-Tae Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hoyoung Maeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yong-Joon Chwae
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Duk Jae Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong-Man Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Woo Ick Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seung-Tae Lee.

Additional information

This investigation was supported by a CMB Yuhan Research Grant of Yonsei University College of Medicine for 2003.

About this article

Cite this article

Lee, ST., Maeng, H., Chwae, YJ. et al. Effect of mesenchymal stem cell transplantation on the engraftment of human hematopoietic stem cells and leukemic cells in mice model. Int J Hematol 87, 327–337 (2008). https://doi.org/10.1007/s12185-008-0041-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-008-0041-3

Keywords

Search

Navigation