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.
Health Phys. 2012 Aug;103(2):138-42. 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.
造血综合征是暴露于高剂量电离辐射后面临的首个治疗挑战。目前，迫切需要确定/开发新的治疗方法，以达到移植阈值。作者提出了一种基于局部和短期分泌选择形态发生素的全局生态位治疗策略的概念，以促进血管生态位，从而提高移植阈值的再生能力，并刺激残留的造血干细胞和祖细胞。本研究旨在建立一种使用 Sonic hedgehog (Shh) 作为第一个候选物的猴基因治疗模型。使用 Amaxa 技术，通过核转染将脂肪组织来源的多能间充质干细胞与模拟和 Sonic hedgehog pIRES2 质粒共转染。全身照射后 48 小时，对 8-Gy γ 照射的猴子进行单次骨髓内注射经处理或未经处理的脂肪干细胞。模拟和 Shh 移植物均耐受良好。这项初步研究确立了瞬时基因治疗在高剂量辐射猴中的可行性。正在进行的研究将确定这种治疗策略的潜在疗效。
