Novel Cell-Based Therapeutic Strategy for Ischemic Colitis with Use of Bone Marrow–Derived Mononuclear Cells in Rats
Novel Cell-Based Therapeutic Strategy for Ischemic Colitis with Use of Bone Marrow–Derived Mononuclear Cells in Rats
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DOI：
10.1007/dcr.0b013e3181a79549
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发表时间：
2009-08
影响因子：
3.9
通讯作者：
A. Tadauchi;Y. Narita;H. Kagami;Y. Niwa;M. Ueda;H. Goto
中科院分区：
文献类型：
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作者：
A. Tadauchi;Y. Narita;H. Kagami;Y. Niwa;M. Ueda;H. Goto
目的：缺血性结肠炎是大肠的常见疾病。在临床环境中，无论采用何种常规治疗，一些患者都会患有难治性缺血性结肠炎。同时，已知骨髓来源的单核细胞会加速新血管形成。本研究旨在验证骨髓源性单核细胞对大鼠缺血性结肠炎的治疗作用。方法：采用部分阻塞直肠、阻断边缘血管的方法建立免疫缺陷大鼠缺血性结肠炎模型。缺血一天后，将来自 Wistar 大鼠的骨髓来源的单核细胞注射到缺血区域（MNC 组）。作为对照，以相同方式注射磷酸盐缓冲盐水（PBS组）。细胞移植后7天，对每只大鼠进行组织学和绞痛运动评估。结果：与组PBS评分相比，MNC组宏观和微观结肠炎严重程度评分均显着降低。此外，MNC组的毛细血管和肌间丛密度显着高于PBS组（分别为9.55±0.74 vs. 4.61±0.22，P<0.01；和8.57±0.41 vs. 5.93±0.31，P<0.02）。与PBS组相比，MNC组的全肠通过时间显着缩短（分别为472.7±17.6分钟和584.8±24.0分钟，P<0.01）。在肠壁的所有层中均检测到移植细胞；然而，这些细胞并没有分化成血管或神经细胞。 结论：这些结果表明，骨髓来源的单核细胞移植不仅可以增强组织再生和血管生成，还可以增强神经发生。骨髓来源的单核细胞移植可能是治疗缺血性结肠炎的有效策略。
PURPOSE:Ischemic colitis is a common disorder of the large bowel. In the clinical setting, some patients suffer refractory ischemic colitis regardless of conventional treatment. Meanwhile, bone marrow–derived mononuclear cells are known to accelerate neovascularization. The purpose of this study was to verify the effects of bone marrow–derived mononuclear cells on ischemic colitis in rats.METHODS:An ischemic colitis model was established by partial obstruction of the rectum and interruption of the marginal vessel in the immunodeficient rat. Bone marrow–derived mononuclear cells from a Wistar rat were injected into the ischemic area one day later than the ischemia (Group MNC). As a control, phosphate-buffered saline was injected in the same manner (Group PBS). Seven days after cell transplantation, each rat was evaluated for histology and colic motility.RESULTS:Compared with Group PBS scores, the Group MNC macroscopic and microscopic colitis severity scores were significantly reduced. Moreover, the density of the capillary and myenteric plexus was significantly higher in Group MNC than in Group PBS (9.55±0.74 vs. 4.61±0.22, respectively, P< 0.01; and 8.57±0.41 vs. 5.93±0.31, respectively, P< 0.02). The whole-gut transit time was significantly shorter in Group MNC compared with Group PBS (472.7±17.6 vs. 584.8±24.0 minutes, respectively, P< 0.01). Transplanted cells were detected in all layers of the intestinal wall; however, these cells did not differentiate into vascular or neural cells.CONCLUSIONS:These results suggest that transplantation of bone marrow–derived mononuclear cells might enhance not only tissue regeneration and angiogenesis but also neurogenesis. Transplantation of bone marrow–derived mononuclear cells may be a useful therapeutic strategy for ischemic colitis.