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Stem cell biology

Mesenchymal stromal cell-derived extracellular vesicles rescue radiation damage to murine marrow hematopoietic cells

Leukemia volume 30, pages 2221–2231 (2016)Cite this article

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Abstract

Mesenchymal stromal cells (MSCs) have been shown to reverse radiation damage to marrow stem cells. We have evaluated the capacity of MSC-derived extracellular vesicles (MSC-EVs) to mitigate radiation injury to marrow stem cells at 4 h to 7 days after irradiation. Significant restoration of marrow stem cell engraftment at 4, 24 and 168 h post irradiation by exposure to MSC-EVs was observed at 3 weeks to 9 months after transplant and further confirmed by secondary engraftment. Intravenous injection of MSC-EVs to 500cGy exposed mice led to partial recovery of peripheral blood counts and restoration of the engraftment of marrow. The murine hematopoietic cell line, FDC-P1 exposed to 500cGy, showed reversal of growth inhibition, DNA damage and apoptosis on exposure to murine or human MSC-EVs. Both murine and human MSC-EVs reverse radiation damage to murine marrow cells and stimulate normal murine marrow stem cell/progenitors to proliferate. A preparation with both exosomes and microvesicles was found to be superior to either microvesicles or exosomes alone. Biologic activity was seen in freshly isolated vesicles and in vesicles stored for up to 6 months in 10% dimethyl sulfoxide at −80 °C. These studies indicate that MSC-EVs can reverse radiation damage to bone marrow stem cells.

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Acknowledgements

This work was supported by the NIH grants 5UH2TR000880, 3UH3TR000880-03S1, 5R01HL103726, 5P20GM103468 and 5T32HL116249. We thank the Flow Cytometry Core at Division of Hematology/Oncology in Rhode Island Hospital, for providing excellent service. We also thank Rebecca Lynn, Research Administrator, for her assistance on this project.

Author contributions

This study was designed, supervised and coordinated by PQ. The manuscript was written by SW, revised by PQ and commented on by all authors. SW designed, performed experiments, collected, analyzed and interpreted data. MD designed and coordinated study. YC and CS performed experiments. EP and YD performed flow cytometry analysis. MDT, MP and AC conducted bleeding animals for engraftment analysis. MD, LG and JA contributed to mice transplantation, DC, SB and FC provided technical advice, and GC gave conceptual advice and GC and DC edited the manuscript.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA

    S Wen, M Dooner, Y Cheng, E Papa, M Del Tatto, M Pereira, Y Deng, L Goldberg, J Aliotta, D Chatterjee, C Stewart & P Quesenberry

  2. Department of Medical Sciences, University of Torino, Torino, Italy

    A Carpanetto, F Collino, S Bruno & G Camussi

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  1. S Wen
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  2. M Dooner
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Wen, S., Dooner, M., Cheng, Y. et al. Mesenchymal stromal cell-derived extracellular vesicles rescue radiation damage to murine marrow hematopoietic cells. Leukemia 30, 2221–2231 (2016). https://doi.org/10.1038/leu.2016.107

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