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Bone Marrow Transplantation

Engraftment capacity of mesenchymal cells following hematopoietic stem cell transplantation in patients receiving reduced-intensity conditioning regimen

Leukemia volume 20, pages 329–335 (2006)Cite this article

Abstract

The engraftment ability of mesenchymal cells was investigated in 26 patients receiving allogeneic transplantation from HLA-identical siblings with reduced-intensity conditioning (RIC). The stem cell source was bone marrow (BM) in eight patients and G-CSF-mobilized peripheral blood hematopoietic cells in 18 cases. A total of 32 patients engrafted very quickly and the chimerism evaluation (both on myeloid and on lymphoid subsets) showed that they were full donor by day 60. At the time of the study they were in complete hematological remission and displayed a full donor hematopoiesis. Two patients showed early disease progression while one did not engraft. Forty-eight out-marrow samples harvested from the 26 patients generated a marrow stromal layer adequate for the chimerism evaluation. Monocyte-macrophage contamination of marrow stromal layers was always reduced below 2% by repeated trypsinizations and treatment with the leucyl-leucine (leu-leu) methyl ester. The chimerism evaluation was performed by PCR analysis of STRs microsatellites and the amelogenin locus, by using capillary electrophoresis (CE) and by FISH analysis in case of the sex mismatch. In eight patients, a partial donor origin of stromal cells was shown (7–86% cells of donor). The source of hematopoietic cells was BM in three patients and mobilized peripheral blood in the other five.

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References

  1. Dexter TM . Stromal cell associated haematopoiesis. J Cell Physiol 1982; 58: 699–706.

    Google Scholar 

  2. Owen M, Friedenstein AJ . Stromal stem cells: marrow-derived osteogenic precursors. CIBA Found Symp 1988; 136: 42–60.

    CAS  PubMed  Google Scholar 

  3. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143–147.

    Article  CAS  PubMed  Google Scholar 

  4. Prockop DJ . Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276: 71–74.

    Article  CAS  PubMed  Google Scholar 

  5. Anklesaria P, Kase K, Glowacki J, Holland CA, Sakakeeny MA, Wright JA 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: 7681–7685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Perkins S, Fleischman RA . Hematopoietic microenvironment: origin, lineage, and transplantability of the stromal cells in long-term bone marrow cultures from chimeric mice. J Clin Invest 1988; 81: 1072–1080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 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: 3041–3051.

    CAS  PubMed  Google Scholar 

  8. El-Badri NS, Wang BY, Cherry, Good RA . Osteoblasts promote engraftment of allogeneic hematopoietic stem cells. Exp Hematol 1998; 26: 110–116.

    CAS  PubMed  Google Scholar 

  9. Keating A, Singer JW, Killen PD, Striker GE, Salo AC, Sanders J et al. Donor origin of the in vitro haematopoietic microenvironment after marrow transplantation in man. Nature 1982; 298: 280–283.

    Article  CAS  PubMed  Google Scholar 

  10. Simmons PJ, Przepiorka D, Thomas ED, Torok-Storb B . Host origin of marrow stromal cells following allogenic bone marrow transplantation. Nature 1987; 328: 429–432.

    Article  CAS  PubMed  Google Scholar 

  11. Laver J, Jhanwar SC, O'Reilly RJ, Castro-Malaspina H . Host origin of the human hematopoietic microenvironment following allogeneic bone marrow transplantation. Blood 1987; 70: 1966–1968.

    CAS  PubMed  Google Scholar 

  12. Agematsu K, Nakahori Y . Recipient origin of bone marrow-derived fibroblastic stromal cells during all periods following bone marrow transplantation in humans. Br J Haematol 1991; 79: 359–365.

    Article  CAS  PubMed  Google Scholar 

  13. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 1999; 5: 309–313.

    Article  CAS  PubMed  Google Scholar 

  14. Koç ON, Peters C, Aubourg P, Raghavan S, Dyhouse S, DeGasperi R 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: 1675–1681.

    Article  PubMed  Google Scholar 

  15. Galotto M, Berisso G, Delfino L, Podesta M, Ottaggio L, Dallorso S et al. Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients. Exp Hematol 1999; 27: 1460–1466.

    Article  CAS  PubMed  Google Scholar 

  16. Cilloni D, Carlo-Stella C, Falzetti F, Summarelli G, Ragazzi E, Colla S et al. Limited engraftment capacity of bone marrow-derived mesenchymal cells following T-cell-depleted hematopoietic stem cell transplantation. Blood 2000; 96: 3637–3643.

    CAS  PubMed  Google Scholar 

  17. Villaron EM, Almeida J, Lopez-Holgado N, Alcoceba M, Sanchez-Abarca LI, Sanchez-Guijo FM et al. Mesenchymal stem cells are present in peripheral blood and can engraft after allogeneic hematopoietic stem cell transplantation. Haematology 2004; 89: 1421–1427.

    Google Scholar 

  18. Castro-Malaspina H, Gay RE, Resnick G, Kapoor N, Meyers P, Chiarieri D et al. Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny. Blood 1980; 56: 289–301.

    CAS  PubMed  Google Scholar 

  19. Thiele DL, Charley MR, Calomeni JA, Lipsky PE . Lethal graft-vs-host disease across major histocompatibility barriers: requirement for leucyl-leucine methyl ester sensitive cytotoxic T cells. J Immunol 1987; 138: 51–57.

    CAS  PubMed  Google Scholar 

  20. Scharf SJ, Smith AG, Hansen JA, McFarland C, Erlich HA . Quantitative determination of bone marrow transplant engraftment using fluorescent polymerase chain reaction primers for human identity markers. Blood 1995; 85: 1954–1963.

    CAS  PubMed  Google Scholar 

  21. Fernandez M, Simon V, Herrera G, Cao C, Del Favero H, Minguell JJ . Detection of stromal cells in peripheral blood progenitor cell collections from breast cancer patients. Bone Marrow Transplant 1997; 20: 265–271.

    Article  CAS  PubMed  Google Scholar 

  22. Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A . Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1994; 1: 71–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zvaifler NJ, Marinova-Mutafchieva L, Adams G, Edwards CJ, Moss J, Burger JA et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res 2000; 2: 477–488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Goan SR, Junghahn I, Wissler M, Becker M, Aumann J, Just U et al. Donor stromal cells from human blood engraft in NOD/SCID mice. Blood 2000; 96: 3971–3978.

    CAS  PubMed  Google Scholar 

  25. Lazarus HM, Haynesworth SE, Gerson SL, Caplan AI . Human bone marrow-derived mesenchymal (stromal) progenitor cells (MPCs) cannot be recovered from peripheral blood progenitor cell collections. J Hematother 1997; 6: 447–455.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Associazione Italiana contro le Leucemie (AIL Ancona), and the Ministry for Education, the Universities and Research (MIUR Ancona), Italy.

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Authors and Affiliations

  1. Department of Hematology, University of Ancona, Ancona, Italy

    A Poloni, P Leoni, F Balducci, R Pasquini, M C Masia & A Olivieri

  2. Department of Legal Medicine, University of Ancona, Ancona, Italy

    L Buscemi & A Tagliabracci

  3. Department of Clinical Immunology, University of Ancona, Ancona, Italy

    N Viola & E Costantino

  4. Unit of Medical Genetic and Prenatal Diagnosis, Ospedale Salesi, Ancona, Italy

    G Discepoli

  5. Division of Hematology-Bone Marrow Transplantation, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy

    P Corradini

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  1. A Poloni
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Correspondence to A Poloni.

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Poloni, A., Leoni, P., Buscemi, L. et al. Engraftment capacity of mesenchymal cells following hematopoietic stem cell transplantation in patients receiving reduced-intensity conditioning regimen. Leukemia 20, 329–335 (2006). https://doi.org/10.1038/sj.leu.2404018

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