骨髓干细胞动员与移植治疗心肌梗死的比较

目的比较骨髓干细胞动员与骨髓单个核细胞移植对兔心肌梗塞的治疗作用,探讨更有效、更适用的干细胞治疗心肌梗塞的方法.方法将30支新西兰白兔采用结扎前降支的方法制作心肌梗塞模型,随机分为动员组、移植组和对照组,动员组(n=10)心梗后3h开始皮下注射粒细胞集落刺激因子(G-CSF)30μg/(kg·d),连续使用5 d,第5天抽取静脉血约10mL,分离单个核细胞(mononudear cells,MNCs)用5-溴脱氧尿嘧啶核苷(bromodeoxyuridine,Brdu)标记后,经静脉注入动物体内.移植组(n=10)心梗后7～10 d,抽取骨髓3～5mL,分离MNCs用Brdu标记,然后开胸将细胞移植至梗死区,对照组(n=10)不采取任何治疗措施.心梗后1周及5周采用超声心动图(UCG)检查了解心脏功能变化,5周时作血液动力学测定,取心脏作免疫组织化学鉴定.结果心梗后5周,动员组左室射血分数(EF)与1周时相比明显增加,移植组无变化,对照组显著下降.5周时动员组及移植组左室舒张末压(LVEDP)、+dp/dtmax和-dp/dtmax与对照组相比均有显著变化.动员组及移植组在心肌梗死区均发现有Brdu标记的阳性细胞,两组梗死区血管密度明显高于对照组,但均未发现有新生的平滑肌细胞及心肌细胞.结论骨髓干细胞动员治疗心肌梗死,能通过促进梗死区血管新生,明显改善心脏功能,骨髓单个核细胞移植可避免心功能的恶化,但在改善心功能方面的作用有限,骨髓干细胞动员可能为心肌梗塞的治疗提供一种更适用的无创性的手段.

Comparison between mobilization and transplantation of bone marrow stem cells for therapy of myocardial infarction in rabbits

Objective] To compare bone marrow stem cells mobilization with bone marrow-derived mononuclear cells (BMCs) transplantation for the therapy of myocardial infarction (MI) in rabbits, explore more practical and effectively stem cells therapeutic strategy for MI. Methods] The 30 rabbits were randomly divided into 3 groups, MI was induced by ligation of the left anterior descending artery. In mobilization group (M, n=10), granulocyte-colony days. On the 5th day the BMCs from 10 mL peripheral blood were labeled with bromodeoxyuridine (BrdU) for 24～48hours, then reinjected intravenously. In transplantation group (T, n=10), BMCs transplantation was performed 5～7days after MI. After being obtained from bone marrow (3～5 mL) of iliac crest and labeled with BrdU for 24～48hours, BMCs were transplanted into infracted myocardium through intramyocardial injection. Control animals (C, n=10) did not receive any treatment after MI. Echocardiography were performed for the evaluation of cardiac function 1 week and 5 weeks after MI, hemodynamic studies and histological study were performed 5 weeks after MI. Results]LV ejection fraction of group M increased significantly, group T had no change, group C decreased 1 week and 5 weeks after MI. Group M and group T had higher LV max +dP/dt and max-dp/dt, lower LV end-diastolic pressure compared with group C 5 weeks after MI. Histological studies revealed that there were BrdU positive cells in the infarcted area of group M and group T, and the density of capillaries group M and group T in the infarcted area was significantly greater in comparison with group C. No regeneration of smooth muscle cells and cardiomyocytes were found in the infarcted area. Conclusion] Bone marrow stem cells mobilization with G-CSF significantly improves the cardiac function for the therapy of MI through angiogenesis in the infarcted area. Transplantation of BMCs can avoid the deterioration of cardiac function, but the efficacy in. amelioration of cardiac function is limited. Bone marrow stem cells mobilization may offer a more practical and non-invasive therapeutic strategy for MI.