title: Gene therapy to mitigate radiation-induced bone marrow aplasia:  preliminary study in highly irradiated monkeys.
abstract: 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.
authors.affiliation: Institut de Recherche Biomédicale des Armées-Centre de Recherche du Service de Santé des Armées, Department of Radiobiology-Cell Therapy Unit, 24 avenue des Maquis du Grésivaudan, 38702, La Tronche, France. micheldrouet@crssa.net
authors.forename: Michel
authors.initials: M
authors.lastname: Drouet
authors.forename: Diane
authors.initials: D
authors.lastname: Agay
authors.forename: Philippe
authors.initials: P
authors.lastname: Garrigou
authors.forename: André
authors.initials: A
authors.lastname: Peinnequin
authors.forename: Francis
authors.initials: F
authors.lastname: Hérodin
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001855:Bone Marrow Diseases / Q000235:genetics* / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D053823:Hedgehog Proteins / Q000235:genetics; D007267:Injections; D008253:Macaca mulatta; D008297:Male; D039902:Multipotent Stem Cells / Q000166:cytology / Q000637:transplantation; D011833:Radiation Injuries, Experimental / Q000235:genetics* / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D053823:Hedgehog Proteins