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Mesenchymal cells generated from patients with myelodysplastic syndromes are devoid of chromosomal clonal markers and support short- and long-term hematopoiesis in vitro

Oncogene volume 24, pages 2441–2448 (2005)Cite this article

Abstract

Myelodysplastic syndromes (MDS) are clonal malignant stem cell disorders characterized by inefficient hematopoiesis. The role of the marrow microenvironment in the pathogenesis of the disease has been controversial and no study has been performed so far to characterize mesenchymal cells (MC) from MDS patients and to analyse their ability to support hematopoiesis. To this end, we have isolated and characterized MC at diagnostic marrow samples (n=12) and have purified their CD34+CD38− and CD34+CD38+ counterparts (n=7) before using MC as a short- and long-term hematopoietic support. We show that MC can be readily isolated from MDS marrow and exhibit a major expansion potential as well as an intact osteoblastic differentiation ability. They do not harbor the abnormal marker identified by FISH in the hematopoietic cells and they stimulate the growth of autologous clonogenic cells. Conversely, highly purified stem cells and their cytokine-expanded progeny harbor the clonal marker with variable frequencies, and both normal and abnormal long-term culture-initiating cell-derived progeny can be effectively supported by autologous MC. Thus, we demonstrate that MDS marrow is an abundant source of MC appearing both cytogenetically and functionally noninvolved by the malignant process and able to support hematopoiesis, suggesting their possible usefulness in future cell therapy approaches.

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Acknowledgements

This work was supported by research grants from the Fondation Contre la Leucémie-Fondation de France to Dr AG Turhan and by a grant from ECOS (Cooperation France–Uruguay) to AG Turhan and C Tourino.

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Authors and Affiliations

  1. Inserm U524, CHU Lille, France

    Valérie Soenen-Cornu, Claude Preudhomme & Pierre Fenaux

  2. Laboratoire d'Hématologie A, CHU Lille, France

    Valérie Soenen-Cornu & Claude Preudhomme

  3. Department of Clinical Biology, Inserm U362, Institut Gustave Roussy, Villejuif, France

    Cristina Tourino, Stéphane Flamant & Ali G Turhan

  4. Translational Research-Cell Therapy Laboratory, Institut Gustave Roussy, Villejuif, France

    Marie-Laure Bonnet, Martine Guillier, Stéphane Flamant & Ali G Turhan

  5. Department of Medicine, Institut Gustave Roussy, Villejuif, France

    Rami Kotb, Jean-Henri Bourhis & Ali G Turhan

  6. Department of Pathology, Institut Gustave Roussy, Villejuif, France

    Alain Bernheim

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  1. Valérie Soenen-Cornu
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  2. Cristina Tourino
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  3. Marie-Laure Bonnet
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  9. Claude Preudhomme
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  10. Pierre Fenaux
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  11. Ali G Turhan
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Correspondence to Ali G Turhan.

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Soenen-Cornu, V., Tourino, C., Bonnet, ML. et al. Mesenchymal cells generated from patients with myelodysplastic syndromes are devoid of chromosomal clonal markers and support short- and long-term hematopoiesis in vitro. Oncogene 24, 2441–2448 (2005). https://doi.org/10.1038/sj.onc.1208405

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