Department of Cardiothoracic Surgery, Stanford, CA 94305, USA.
J Heart Lung Transplant. 2009 Nov;28(11):1158-1165.e1. doi: 10.1016/j.healun.2009.06.018. Epub 2009 Sep 26.
Autologous bone marrow mononuclear cell (BMMC) therapy has shown promise for improving cardiac function after myocardial infarction. The efficiency of such therapy for diabetic patients remains unknown.
BMMCs were harvested from type 2 diabetic male BKS.Cg-m+/+Lepr(db)/J mice or C57BLKS/J (non-diabetic control) mice and were isolated using Ficoll-based separation. Cell characterization was performed by flow cytometry. Cell viability was determined by apoptosis and proliferation assays. Female BKS.Cg-m+/+Lepr(db)/J mice underwent left anterior descending artery ligation and were randomized into 3 groups receiving 2.5 x 10(6) diabetic BMMCs (n = 8), 2.5 x 10(6) control BMMCs (n = 8), or phosphate-buffered saline (n = 6). At Week 5, cardiac function was assessed with echocardiography and invasive hemodynamic measurements. Post-mortem cell survival was quantified by TaqMan real-time transcription polymerase chain reaction (RT-PCR) for the male Sry gene.
BKS.Cg-m+/+Lepr(db)/J BMMCs showed a significantly lower mononuclear fraction and a significantly lower proliferation rate compared with C57BLKS/J BMMCs. Fractional shorting (40.1% +/- 1.2% vs 30.3% +/- 1.9%; p = 0.001) and cardiac output (4,166 +/- 393 vs 2,246 +/- 462 microl/min; p = 0.016) significantly improved for mice treated with control BMMCs injection compared with those treated with diabetic BMMCs, respectively. This difference could not be attributed to difference in cell engraftment because TaqMan RT-PCR showed no significant difference in cell survival in infarcted hearts between the 2 groups.
Diabetic BMMCs are significantly impaired in their ability to improve cardiac function after myocardial infarction compared with control BMMCs. These findings could have significant clinical implication regarding autologous BMMC therapy in diabetic patients.
自体骨髓单个核细胞（BMMC）治疗在改善心肌梗死后心功能方面显示出良好的前景。然而，这种治疗方法在糖尿病患者中的疗效尚不清楚。
从 2 型糖尿病雄性 BKS.Cg-m+/+Lepr(db)/J 小鼠或 C57BLKS/J（非糖尿病对照）小鼠中提取 BMMC，并用 Ficoll 分离法分离。通过流式细胞术进行细胞特征鉴定。通过凋亡和增殖试验测定细胞活力。雌性 BKS.Cg-m+/+Lepr(db)/J 小鼠接受左前降支结扎，并随机分为 3 组，分别接受 2.5×10(6)糖尿病 BMMC（n=8）、2.5×10(6)对照 BMMC（n=8）或磷酸盐缓冲盐水（n=6）。在第 5 周，通过超声心动图和侵入性血流动力学测量评估心功能。通过 TaqMan 实时转录聚合酶链反应（RT-PCR）对雄性 Sry 基因定量检测死后细胞存活情况。
与 C57BLKS/J BMMC 相比，BKS.Cg-m+/+Lepr(db)/J BMMC 的单核细胞分数明显较低，增殖率明显较低。与接受糖尿病 BMMC 治疗的小鼠相比，接受对照 BMMC 注射治疗的小鼠的短轴缩短率（40.1%±1.2%比 30.3%±1.9%；p=0.001）和心输出量（4,166±393 比 2,246±462 μl/min；p=0.016）显著改善。这种差异不能归因于细胞移植的差异，因为 TaqMan RT-PCR 显示两组在梗死心脏中的细胞存活没有显著差异。
与对照 BMMC 相比，糖尿病 BMMC 在改善心肌梗死后心功能方面的能力明显受损。这些发现对于糖尿病患者的自体 BMMC 治疗具有重要的临床意义。
