骨髓间质干细胞移植治疗DKO鼠后肌组织的超微结构改变

Ultrastructural changes in muscular tissues of dystrophin/utrophin double-knockout mice after bone marrow-derived mesenchymal stem cell transplantation

目的观察Duchenne型肌营养不良症模型DKO小鼠经骨髓间质干细胞(MSC)移植治疗后肌组织的超微结构改变情况。方法用体外培养纯化的第五代SD大鼠MSC经尾静脉移植治疗DKO鼠,在移植后15 w取鼠后肢腓肠肌组织进行透射电镜超微结构的观察。结果传5代后的MSC均一性好,免疫源性低;移植治疗后DKO鼠的运动功能有所改善,生存时间也有延长。肌组织的超微结构观察发现,肌细胞膜断裂、膜下组织分离水肿、核中移、局部肌原纤维松散、炎症细胞浸润和结缔组织增生等病变情况较对照鼠有改善,并出现肌膜下多个幼稚核融合现象。结论MSC具有强大的可塑性,通过血循环可趋向病变肌组织并参与鼠肌萎缩组织的修复与再生作用。

Objective To observe the ultrastructural changes in the muscular tissues of Duchenne muscular dystrophy mouse models with dystrophin/utrophin double-knockout (DKO) after transplantation of bone marrow-derived mesenchymal stem cells (MSCs). Methods The fifth passage of in vitro cultured MSCs from SD rats were transplanted into the DKO mice via the tail vein, and the ultrastructural changes in the gastrocnemius of the recipient rats were observed using transmission electron microscope 15 weeks after the transplantation. Results The fifth passage of the in vitro cultured MSCs growing in colonies possessed good homogeneity with low immunogenic activity for transplantation via the tail vein. After transplantation, the DKO mice exhibited improved motor function and prolonged survival period. Ultrastructural observation of the gastrocnemius of the recipient DKO mice revealed much alleviated sarcolemmal disruption, dissociation and edema of the subsarcolemmal tissues, central nuclear shift, loosening of the local myofibrils, inflammatory cell infiltration and connective tissue hyperplasia in comparison with the tissues from the DKO mice without MSC transplantation. Fusion of several immature nuclei was observed in the subsarcolemmal region. Conclusions MSCs possess strong plasticity in vitro and in vivo, and after transplantation, the MSCs may migrate to lesioned muscular tissues via the blood circulation to participate in the repair and regeneration the atrophied muscular tissues.