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Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy

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Abstract

Hematopoietic recovery after high-dose chemotherapy (HDC) in the treatment of hematological diseases may be slow and/or incomplete. This is generally attributed to progressive hematopoietic stem cell failure, although defective hematopoiesis may be in part due to poor stromal function. Chemotherapy is known to damage mature bone marrow stromal cells in vitro, but the extent to which marrow mesenchymal stem cells (MSCs) are damaged by HDC in vivo is largely unknown. To address this question, the phenotype and functional properties of marrow MSCs derived from untreated and chemotherapeutically treated patients with hematological malignancy were compared. This study demonstrates a significant reduction in MSC expansion and MSC CD44 expression by MSCs derived from patients receiving HDC regimens, thus implicating potential disadvantages in the use of autologous MSCs in chemotherapeutically pretreated patients for future therapeutic strategies. The clinical importance of these HDC-induced defects we have observed could be determined through prospective randomized trials of the effects of MSC cotransplantation on hematopoietic recovery in the setting of HDC with and without hematopoietic stem cell rescue.

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Acknowledgements

We wish to express our gratitude to the doctors and nurses at the Royal United Hospital, Bath, for bone marrow collections and helpful discussions and to all patients who donated marrow samples. We would also like to thank midwifes at the Central Delivery Suite, Southmead Hospital, Bristol, for cord blood collections and mothers who donated cord blood. This work was supported by a Ph.D. bursary from the University of the West of England and also in part by the funding provided by the Transplant Trust.

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Authors and Affiliations

  1. Center for Research in Biomedicine, Faculty of Applied Sciences, University of the West of England, Bristol, UK

    Kevin Kemp, Ruth Morse, Jill Hows & Craig Donaldson

  2. Department of Hematology, Royal United Hospital, Bath, UK

    Sarah Wexler & Christine Cox

  3. Multiple Sclerosis and Stem Cell Group, Institute of Clinical Neurosciences, Clinical Sciences North Bristol, University of Bristol, Bristol, UK

    Elizabeth Mallam

  4. MS Group, 1st Floor, The Burden Center, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, BS16 1JB, UK

    Kevin Kemp

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  1. Kevin Kemp
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Correspondence to Kevin Kemp.

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Kemp, K., Morse, R., Wexler, S. et al. Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy. Ann Hematol 89, 701–713 (2010). https://doi.org/10.1007/s00277-009-0896-2

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  • DOI: https://doi.org/10.1007/s00277-009-0896-2

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