RESUMO
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.
Assuntos
Doenças da Medula Óssea/genética , Doenças da Medula Óssea/terapia , Terapia Genética/métodos , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/terapia , Adipócitos/citologia , Animais , Proteínas Hedgehog/genética , Injeções , Macaca mulatta , Masculino , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/transplante , Resultado do TratamentoRESUMO
Multicytokine therapy may be useful to counteract radiation-induced myelosuppression. We assessed the stem cell factor + glycosylated erythropoietin + pegylated granulocyte colony-stimulating factor combination (SEG) as an emergency treatment. SEG in highly irradiated monkeys efficacy appeared to be restricted to granulopoiesis. Early administration of Erythropoietin did not prevent radiation-induced anemia.
