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Stromal Cells

W/Wv marrow stromal cells engraft and enhance early erythropoietic progenitors in unconditioned Sl/Sld murine recipients

Bone Marrow Transplantation volume 30, pages 867–872 (2002)Cite this article

Abstract

Transplantation of marrow stromal cells may provide a means of modulating hematopoiesis and serve as a form of cell therapy. We employed a murine transplant model using Sl/Sld mice, which have macrocytic anemia due to defective expression of stem cell factor (SCF) on bone marrow stromal cells. Donor cells were derived from the complementary mutant strain W/Wv, which also exhibit anemia, due to mutations in c-kit, the SCF receptor expressed on hematopoietic stem cells. The strength of this model is that any correction of the Sl/Sld anemia from the infusion of W/Wv stromal cells can be attributed to the effect of the stromal cells and not to contaminating W/Wv hematopoietic stem cells, a major concern in experiments involving wild-type animals. Cultured stromal cells were infused into unconditioned non-splenectomized Sl/Sld mice. Engraftment of donor stromal cells reached levels of up to 1.0% of total marrow cells 4 months post transplant. However, stromal engraftment was not detectable in the spleen. Recipients of W/Wv stroma showed a significant increase in the committed erythroid progenitors compared with those receiving Sl/Sld stromal cells: 109 ± 26 vs 68 ± 5 CFU-E per 105 BMC, P = 0.002; 25 ± 10 vs15 ± 5 BFU-E per 105 BMC, P = 0.037, for W/Wv and Sl/Sld stroma recipients, respectively. Despite this increase in erythroid progenitors, the anemia was not corrected. Our data suggest that in this murine model, splenic erythropoiesis may influence stromal cell therapy, and that higher levels of marrow engraftment may be necessary to obtain a clinically significant effect.

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Acknowledgements

Armand Keating holds the Gloria and Seymour Epstein Chair in Cell Therapy and Transplantation at the University of Toronto and the University Health Network.

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Author notes

  1. BR Clark

    Present address: City of Hope National Medical Center, Duarte, CA, USA

Authors and Affiliations

  1. Toronto General Research Institute, Toronto, ON, Canada

    SJ Bubnic, X-H Wang, BR Clark & A Keating

  2. Princess Margaret Hospital/Ontario Cancer Institute, Toronto, ON, Canada

    A Keating

  3. Institute of Medical Science, University of Toronto, Toronto, ON, Canada

    SJ Bubnic & A Keating

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Bubnic, S., Wang, XH., Clark, B. et al. W/Wv marrow stromal cells engraft and enhance early erythropoietic progenitors in unconditioned Sl/Sld murine recipients. Bone Marrow Transplant 30, 867–872 (2002). https://doi.org/10.1038/sj.bmt.1703761

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