非黏附骨髓源干细胞治疗急性放射损伤

Therapeutic potential of non-adherent bone marrow-derived stem cells for acute radiation injury

背景: 目前对于辐射剂量超过8Gy的急性放射病尚缺乏有效的治疗方案,间充质干细胞可以分泌多种造血因子、重建造血,在放射损伤救治中具有重要意义。目的: 探讨非黏附骨髓源干细胞在8.5GyX射线照射所致急性骨髓型放射损伤救治中的作用及作用机制。方法: 取胎儿四肢长骨的非黏附骨髓源干细胞,分析其麦面抗原,细胞周期,成骨和成脂分化潜能,以及血管内皮生长因子及AnnexinA2表达。BALB/C小鼠受8.5Gy一次性全身均匀X射线照射后随机分成骨髓源干细胞组和对照组,骨髓源干细胞组小鼠在X射线照射2h内经尾静脉输注含3×106CFDA-SE标记的人非黏附骨髓源干细胞的细胞悬液0.3mL,对照组小鼠在X射线照射2h内输注0.3mL生理盐水。观察骨髓源干细胞的分布情况、小鼠的存活率、白细胞变化、骨髓病理变化及骨髓中新生血管形成情况。结果与结论: X射线照射后移植的非黏附间充质干细胞可以向损伤部位归巢;骨髓源干细胞组小鼠存活率明显高于对照组;与对照组相比,骨髓源干细胞组小鼠外周血白细胞计数下降慢且恢复迅速,X射线照射后14d左右达最低,30d基本恢复至正常水平。X射线照射后21d,骨髓源干细胞组骨髓增生活跃,骨髓腔内新生造血灶显著多于对照,血管密度亦显著高于对照组。说明人胎儿非黏附骨髓源干细胞促进急性放射损伤小鼠骨髓内新生血管形成,改善并加快受损小鼠造血功能的恢复。

OBJECTIVE： To investigate the therapeutic potential of non-adherent bone marrow-derived stern cells in the treatment of acute radiation injury induced by 8.5 Gy X-ray irradiation, as well as the mechanisms involved. METHODS： Non-adherent marrow-derived stem cells from the long bone of fetal limbs were collected for analyzing surface antigens, cell cycle, osteogenic and adipogenic differentiation potential, and expressions of vascular endothelial growth factors and Annexin A2. After being exposed to 8.5 Gy total body irradiation, BALB/C mice were randomly assigned into transplantation group and control group. Mice in the transplantation group were given 3x108 CFDA-SE labeled human non-adherent bone marrow-derived stem cells, and those in thecontrol group were given 0.3 mL normal saline. Then, the survival rate, peripheral white blood cells at different time, pathologic change and angiogenesis of the bone marrow were observed. RESULTS AND CONCLUSION： After X-ray irradiation, transplanted non-adherent mesenchymal stem cells appeared to have a homing to the site of injury. The survival rate of mice in the transplantation group was much higher than that in the control group. Compared with the control group, the white blood cells in the transplantation group decreased more slowly while recovered more rapid： the nadir appeared at day 14 after transplantation while it recovered within 30 days. The bone marrow of mice in the transplantation group regenerated more actively and had more hematopoietic islands than those in the control group on day 21. In addition, bone marrow angiogenesis of the transplantation group was more obvious than that of the control group. In conclusion, human fetal non-adherent bone marrow-derived stem cells could promote bone marrow angiogenesis in a mouse model of acute radiation injury, through which they could play an important role in tissue regeneration of acute radiation injury.