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Gene Therapy to Mitigate Radiation-Induced Bone Marrow Aplasia: Preliminary Study in Highly Irradiated Monkeys

Drouet, Michel; Agay, Diane; Garrigou, Philippe; Peinnequin, André; Hérodin, Francis

doi: 10.1097/HP.0b013e3182475a93

The hematopoietic syndrome represents the first therapeutic challenge following exposure to high doses of ionizing radiation. Today there is a crucial need to identify/develop new treatments in order to reach the transplantation threshold. The authors propose the concept of a global niche therapy strategy based on local and short-term secretion of selected morphogenes to favor a vascular niche in order to raise the transplantation threshold regeneration and to stimulate residual hematopoietic stem and progenitor cells. The present study was aimed at setting up a monkey model of gene therapy using Sonic hedgehog (Shh) as a first candidate. Multipotent mesenchymal stem cells from adipocyte tissues were nucleofected with mock and Sonic hedgehog pIRES2 plasmids using Amaxa technology. 8-Gy gamma irradiated monkeys were given a single intraosseous injection of manipulated or unmanipulated adipocyte stem cells 48 h following total body irradiation. Mock and Shh-grafts were well tolerated. This preliminary study establishes the feasibility of transient gene therapy in highly irradiated monkeys. Ongoing studies will determine the putative efficacy of this therapeutic strategy.

Health Phys. 103(2):138Y142; 2012

*Institut de Recherche Biomédicale des Armées-Centre de Recherche du Service de Santé des Armées (IRBA-CRSSA), Department of Radiobiology-Cell Therapy Unit, 24 avenue des Maquis du Grésivaudan, 38702, La Tronche, France.

The authors declare no conflict of interest.

For correspondence contact: Michel Drouet, IRBA-antenne la Tronche-CRSSA, or email at

(Manuscript accepted 19 December 2011)

© 2012 by the Health Physics Society