Biology of Blood and Marrow Transplantation
Volume 17, Issue 2 , Pages 214-225 , February 2011

Mesenchymal Stromal Cells Fail to Prevent Acute Graft-versus-Host Disease and Graft Rejection after Dog Leukocyte Antigen-Haploidentical Bone Marrow Transplantation

  • Marco Mielcarek

      Affiliations

    • Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • Department of Medicine, University of Washington, Seattle, Washington
    • Corresponding Author InformationCorrespondence and reprint requests: Marco Mielcarek, MD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, PO Box 19024 Seattle, WA 98109.
    • ,
  • Rainer Storb

      Affiliations

    • Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • Department of Medicine, University of Washington, Seattle, Washington
    • ,
  • George E. Georges

      Affiliations

    • Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • Department of Medicine, University of Washington, Seattle, Washington
    • ,
  • Ludmila Golubev

      Affiliations

    • Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • ,
  • Alla Nikitine

      Affiliations

    • Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • ,
  • Billanna Hwang

      Affiliations

    • Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • ,
  • Richard A. Nash

      Affiliations

    • Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • Department of Medicine, University of Washington, Seattle, Washington
    • ,
  • Beverly Torok-Storb

      Affiliations

    • Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington

Received 26 May 2010 ,Accepted 19 August 2010.

References 

  1. 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;30:42–48
  2. Le Blanc K, Tammik L, Sundberg B, et al. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol. 2003;57:11–20
  3. Krampera M, Glennie S, Dyson J, et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood. 2003;101:3722–3729
  4. Sudres M, Norol F, Trenado A, et al. Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J Immunol. 2006;176:7761–7767
  5. Chung NG, Jeong DC, Park SJ, et al. Cotransplantation of marrow stromal cells may prevent lethal graft-versus-host disease in major histocompatibility complex–mismatched murine hematopoietic stem cell transplantation. Int J Hematol. 2004;80:370–376
  6. Tisato V, Naresh K, Girdlestone J, et al. Mesenchymal stem cells of cord blood origin are effective at preventing but not treating graft-versus-host disease. Leukemia. 2007;21:1992–1999
  7. Lazarus HM, Koc ON, Devine SM, et al. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant. 2005;11:389–398
  8. in’t Anker PS, Noort WA, Kruisselbrink AB, et al. Nonexpanded primary lung and bone marrow–derived mesenchymal cells promote the engraftment of umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol. 2003;31:881–889
  9. Angelopoulou M, Novelli E, Grove JE, et al. Cotransplantation of human mesenchymal stem cells enhances human myelopoiesis and megakaryocytopoiesis in NOD/SCID mice. Exp Hematol. 2003;31:413–420
  10. Le Blanc K, Samuelsson H, Gustafsson B, et al. Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia. 2007;21:1733–1738
  11. Lee ST, Jang JH, Cheong JW, et al. Treatment of high-risk acute myelogenous leukaemia by myeloablative chemoradiotherapy followed by co-infusion of T cell–depleted haematopoietic stem cells and culture-expanded marrow mesenchymal stem cells from a related donor with one fully mismatched human leucocyte antigen haplotype. Br J Haematol. 2002;118:1128–1131
  12. Lee WS, Suzuki Y, Graves SS, Iwata M, Venkataraman GM, Mielcarek M, et al. Canine bone marrow-derived mesenchymal stromal cells suppress allo-reactive lymphocyte proliferation in vitro but fail to enhance engraftment in canine bone marrow transplantation. Biology of Blood and Marrow Transplantation. 2010;[Epub ahead of print]
  13. Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third-party haploidentical mesenchymal stem cells. Lancet. 2004;363:1439–1441
  14. Lazarus HM, Haynesworth SE, Gerson SL, et al. Ex vivo expansion and subsequent infusion of human bone marrow–derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant. 1995;16:557–564
  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;18:307–316
  16. Ringdén O, Uzunel M, Rasmusson I, et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation. 2006;81:1390–1397
  17. Le Blanc K, Frassoni F, Ball L, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579–1586
  18. Baron F, Lechanteur C, Willems E, et al. Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transplant. 2010 Jun;16(6):838–847Epub 2010 Jan 28
  19. Martin PJ, Uberti JP, Soiffer RJ, et al. Prochymal improves response rates in patioents with steroid-refractory acute graft versus host disease (SR-GVHD) involving the liver and gut: results of a randomized, placebo-controlled, multicenter phase III trial in GVHD. [abstract] Biol Blood Marrow Transplant. 2010;16(Suppl):41
  20. Roecklein BA, Torok-Storb B. Functionally distinct human marrow stromal cell lines immortalized by transduction with the human papilloma virus E6/E7 genes. Blood. 1995;85:997–1005
  21. Graf L, Iwata M, Torok-Storb B. Gene expression profiling of the functionally distinct human bone marrow stromal cell lines HS-5 and HS-27a. [letter] Blood. 2002;100:1509–1511
  22. Gartner SM, Kaplan HS. Long-term culture of human bone marrow cells. Proc Natl Acad Sci U S A. 1980;77:4756–4759
  23. Raff RF, Storb R, Ladiges WC, et al. Recognition of target cell determinants associated with DLA-D locus–encoded antigens by canine cytotoxic lymphocytes. Transplantation. 1985;40:323–328
  24. Burroughs L, Mielcarek M, Little M-T, et al. Durable engraftment of AMD3100-mobilized autologous and allogeneic peripheral blood mononuclear cells in a canine transplantation model. Blood. 2005;106:4002–4008
  25. Wagner JL, Burnett RC, DeRose SA, et al. Histocompatibility testing of dog families with highly polymorphic microsatellite markers. Transplantation. 1996;62:876–877
  26. Wagner JL, Works JD, Storb R. DLA-DRB1 and DLA-DQB1 histocompatibility typing by PCR-SSCP and sequencing. Tissue Antigens. 1998;52:397–401
  27. Mielcarek M, Roecklein BA, Torok-Storb B. CD14+ cells in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells induce secretion of interleukin-6 and G-CSF by marrow stroma. Blood. 1996;87:574–580
  28. Mielcarek M, Georges GE, Storb R. Denileukin difitoxin as prophylaxis against graft-versus-host disease in the canine hematopoietic cell transplantation model. Biol Blood Marrow Transplant. 2006;12:899–904
  29. Georges GE, Storb R, Bruno B, et al. Engraftment of DLA-haploidentical marrow with ex vivo expanded, retrovirally transduced cytotoxic T lymphocytes. Blood. 2001;98:3447–3455
  30. Yu C, Ostrander E, Bryant E, et al. Use of (CA)n polymorphisms to determine the origin of blood cells after allogeneic canine marrow grafting. Transplantation. 1994;58:701–706
  31. Hilgendorf I, Weirich V, Zeng L, et al. Canine haematopoietic chimerism analyses by semiquantitative fluorescence detection of variable number of tandem repeat polymorphism. Vet Res Commun. 2005;29:103–110
  32. Bindslev L, Haack-Sorensen M, Bisgaard K, et al. Labelling of human mesenchymal stem cells with indium-111 for SPECT imaging: effect on cell proliferation and differentiation. Eur J Nucl Med Mol Imag. 2006;33:1171–1177
  33. Keating A. Mesenchymal stromal cells. Curr Opin Hematol. 2006;13:419–425
  34. Bernardo ME, Locatelli F, Fibbe WE. Mesenchymal stromal cells. Ann NY Acad Sci. 2009;1176:101–117
  35. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105:1815–1822
  36. Meisel R, Zibert A, Laryea M, et al. Human bone marrow stromal cells inhibit allogeneic T cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood. 2004;103:4619–4621
  37. Rasmusson I, Ringden O, Sundberg B, et al. Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp Cell Res. 2005;305:33–41
  38. Gao J, Dennis JE, Muzic RF, et al. The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs. 2001;169:12–20
  39. Chin BB, Nakamoto Y, Bulte JW, et al. 111In oxine–labeled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction. Nucl Med Commun. 2003;24:1149–1154

 Financial disclosure: See Acknowledgments on page 224.

PII: S1083-8791(10)00364-2

doi: 10.1016/j.bbmt.2010.08.015

Biology of Blood and Marrow Transplantation
Volume 17, Issue 2 , Pages 214-225 , February 2011

Article Tools

* Image Usage & Resolution