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Pre-clinical Studies

Short-term sonic-hedgehog gene therapy to mitigate myelosuppression in highly irradiated monkeys: hype or reality?

Bone Marrow Transplantation volume 49, pages 304–309 (2014)Cite this article

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Abstract

The protection of hematopoietic stem and progenitor cells and their environment is required for recovery from radiation-induced (RI) myelosuppression. To achieve this goal, we propose a new gene therapy strategy based on local and short-term synthesis and expression of Sonic hedgehog morphogene (Shh) at the niche level. We investigated the hematopoietic response of 8 Gy gamma-irradiated monkeys to a single intra-osseous injection of multipotent mesenchymal stem cells (adipocyte-derived stem cells/ASC) transduced with a Shh pIRES2 plasmid (3+/−0.4 × 106 cells/kg on day (D) 2; n=4). Control animals were injected with mock-ASCs (n=4). Two controls died from radiation toxicity on D19 and D196, whereas all Shh-ASC treated monkeys fully recovered. Thrombocytopenia (4.75+/−1.8 days versus 10+/−2.2 days, platelet count <20 × 109/L), neutropenia (14.2 +/−1 days versus 17.7 +/−2.6 days, ANC count<0.5 × 109/L) and anemia (15.5 +/−3.6 days versus 50.7 +/−31 days, Hb less than 10 g/dL) duration were reduced in Shh-ASC animals. Areas under the curve of platelets (P<0.05), ANCs (P=0.06) and RBC/Hb between D0 and D30 were higher in Shh-ASC injected animals. Globally this study suggests that Shh may represent a new factor to counteract RI-myelosuppression.

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Acknowledgements

The authors thank Diane Agay, Bruno Ballester, Nancy Grenier and Hervé Chaussard for their technical assistance. This work was supported by a Grant from Direction Générale de l’Armement.

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  1. Department of Radiobiology, Institut de Recherche Biomédicale des Armées, BP73, Brétigny-sur-Orge, France

    M Drouet, P Garrigou, A Peinnequin & F Hérodin

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  1. M Drouet
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  2. P Garrigou
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  4. F Hérodin
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Correspondence to M Drouet.

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Drouet, M., Garrigou, P., Peinnequin, A. et al. Short-term sonic-hedgehog gene therapy to mitigate myelosuppression in highly irradiated monkeys: hype or reality?. Bone Marrow Transplant 49, 304–309 (2014). https://doi.org/10.1038/bmt.2013.162

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