促红细胞生成素和羊膜间充质干细胞协同治疗促进脊髓损伤再生

目的 观察促红细胞生成素和羊膜间充质干细胞对脊髓损伤(SCI)的综合治疗效应.方法 60只SD大鼠在T11水平进行脊髓半切术,形成2mm缺损.羊膜间充质干细胞(促红细胞生成素协同治疗为Ⅳ组,无促红细胞生成素协同治疗为Ⅲ组),生理盐水(促红细胞生成素协同治疗为Ⅱ组,无促红细胞生成素的为Ⅰ组)移植入缺损处.用损伤后3个月内的临床运动评分,8周时的细胞增殖、免疫组织化学结果 评价脊髓的修复.结果 临床运动评分,Ⅳ组(12.01±0.62)恢复优于Ⅲ组(9.47±0.36)、Ⅱ组(7.57±0.28),差异有统计学意义(P<0.01).并且Ⅳ组损伤区具有更高密度的5-溴脱氧尿嘧啶核苷(BrdU)阳性细胞(25.34±3.51),损伤脊髓远端有更高水平的抗微管相关蛋白-2(MAP-2)表达(8.47±0.87),其差异有统计学意义(P<0.01).结论 促红细胞生成素和羊膜间充质干细胞对于脊髓损伤有协同治疗作用.

Abstract：

Objective To evaluate the combined effects of erythropoietin and amnion-derived mesenchymal stem cells on spinal cord injury (SCI).Methods In 60 SD rats (n=15 in each group) transverse hemi-section at the T11 level was carried out, leaving an approximately 2-mm gap between the distal and proximal ends of the cord. Amnion-derived mesenchymal stem cells embedded in fibrin glue treated with or without erythropoietin (groups Ⅲ and Ⅳ) or fibrin glue with or without erythropoietin (groups Ⅰ and Ⅱ) were transplanted into the gap in the injured spinal cord. Spinal cord regeneration was assessed using a clinical locomotor rating scale scores (BBB scores) every week after injury, and immunohistochemistry 8 weeks after injury.Results Regeneration was more advanced in group Ⅳ (12.01±0.62) than in groups Ⅲ (9.47±0.36) or Ⅱ (7.57±0.28) according to the clinical motor score (P<0.01). Higher densities of bromodeoxyuridine (25.34±3.51) in the injured area and higher expression levels of MAP-2 (8.47±0.87) over the distal end of the injured spinal cord were observed in group Ⅳ than in groups Ⅱ or Ⅲ (P<0.01).Conclusion This synergy between erythropoietin and amnion-derived mesenchymal stem cells may be due to increased proliferation of progenitor cells in the injured area and increased expression of neuronal stem cell markers in the distal end of the injured cord.

Enhanced regeneration in spinal cord injury by concomitant treatment with erythropoietin and amnion-derived mesenchymal stem cells

Objective To evaluate the combined effects of erythropoietin and amnion-derived mesenchymal stem cells on spinal cord injury (SCI).Methods In 60 SD rats (n=15 in each group) transverse hemi-section at the T11 level was carried out, leaving an approximately 2-mm gap between the distal and proximal ends of the cord. Amnion-derived mesenchymal stem cells embedded in fibrin glue treated with or without erythropoietin (groups Ⅲ and Ⅳ) or fibrin glue with or without erythropoietin (groups Ⅰ and Ⅱ) were transplanted into the gap in the injured spinal cord. Spinal cord regeneration was assessed using a clinical locomotor rating scale scores (BBB scores) every week after injury, and immunohistochemistry 8 weeks after injury.Results Regeneration was more advanced in group Ⅳ (12.01±0.62) than in groups Ⅲ (9.47±0.36) or Ⅱ (7.57±0.28) according to the clinical motor score (P<0.01). Higher densities of bromodeoxyuridine (25.34±3.51) in the injured area and higher expression levels of MAP-2 (8.47±0.87) over the distal end of the injured spinal cord were observed in group Ⅳ than in groups Ⅱ or Ⅲ (P<0.01).Conclusion This synergy between erythropoietin and amnion-derived mesenchymal stem cells may be due to increased proliferation of progenitor cells in the injured area and increased expression of neuronal stem cell markers in the distal end of the injured cord.