*Institut de Recherche Biomédicale des Armées (IRBA), Département des Effets Biologiques des Rayonnements, BP 73, Brétigny sur Orge Cedex, France; †Institut für Radiobiologie der Bundeswehr, Neuherbergstraße 11, 80937 München, Germany.
Health Phys. 2014 Jun;106(6):713-9. doi: 10.1097/HP.0000000000000099.
Cutaneous radiation syndrome is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Adipocyte derived stem cells injection may improve tissue regeneration through secreted factors. Thus mesenchymal stem cells secretome optimization, using transient transfection, may represent a new strategy to treat this syndrome. Sonic hedgehog, a secreted protein involved in cell proliferation and angiogenesis, has been chosen as a first candidate. Here preliminary results are reported of the therapeutic potential of transient gene therapy to cure cutaneous radiation syndrome in a minipig model. Adipocyte derived stem cells were transiently transfected by electroporation with a plasmid coding for Sonic Hedgehog. Göttingen minipigs were locally irradiated using a (60)Co gamma source at the dose of 50 Gy and received Phosphate Buffer Salin (controls: n = 8), stem cells (50 × 10⁶ each time, n = 5) or transfected stem cells (25±7 × 10⁶ each time, n = 1). All controls exhibited a homogeneous clinical evolution of cutaneous radiation syndrome with final necrosis (day 91). In stem cell injected minipigs, an ultimate wound healing was observed in four out of five grafted animals (day 130 ± 28, complete in two of them) (historical results). The Sonic hedgehog animal, albeit injected with a lower number of transfected stem cells, presented a very similar evolution of skin healing without necrosis or uncontrolble pain. Globally this preliminary report suggests that local injection of Sonic Hedgehog transfected adipocyte derived stem cells may improve wound healing. Thus work is ongoing to evaluate this therapeutic strategy on a larger number of animals.
皮肤辐射综合征是局部皮肤暴露于高剂量电离辐射后的延迟后果。脂肪细胞衍生的干细胞注射可能通过分泌因子改善组织再生。因此，使用瞬时转染优化间充质干细胞分泌组，可能代表治疗这种综合征的一种新策略。Sonic Hedgehog 是一种参与细胞增殖和血管生成的分泌蛋白，已被选为第一个候选者。这里报道了瞬时基因治疗在小型猪模型中治疗皮肤辐射综合征的治疗潜力的初步结果。脂肪细胞衍生的干细胞通过电穿孔瞬时转染编码 Sonic Hedgehog 的质粒。使用 (60)Co γ源在 50 Gy 的剂量下对哥廷根小型猪进行局部照射，并用磷酸盐缓冲盐水（对照组：n = 8）、干细胞（每次 50 × 10⁶）或转染的干细胞（每次 25±7 × 10⁶）处理（n = 1）。所有对照动物均表现出皮肤辐射综合征的均匀临床演变，最终发生坏死（第 91 天）。在注射干细胞的小型猪中，五头移植动物中有四头最终伤口愈合（第 130 ± 28 天，其中两例完全愈合）（历史结果）。尽管注射了数量较少的转染干细胞，但 Sonic Hedgehog 动物的皮肤愈合演变非常相似，没有坏死或无法控制的疼痛。总的来说，本初步报告表明，局部注射 Sonic Hedgehog 转染的脂肪细胞衍生干细胞可能改善伤口愈合。因此，正在进行更多动物的评估这项治疗策略的工作。
