Cell Transplantation：干细胞来源影响治疗心肌梗塞

当来自丹麦和瑞典的一个研究小组比较了从一名84岁的患有缺血性冠状动脉疾病(ischemic coronary disease)的男性供者体内获得的脂肪干细胞(adipose-derived stem cells, ASCs)和骨髓干细胞(bone marrow-derived stem cells, BMSCs)再生性治疗心肌梗塞模式大鼠的疗效时,他们发现尽管这两种类型的干细胞并不诱导心肌血管新生,但是ASCs更多地保护实验大鼠的心脏功能.相关研究结果于2012年12月4日免费地在线发表在Cell Transplantation期刊上,论文标题为"Comparison Of Human Adipose-Derived Stem Cells And Bone Marrow-Derived Stem Cells In A Myocardial Infarction Model".

论文共同作者Trine Fink博士说,"利用骨髓间充质干细胞(bone marrow-derived mesenchymal stem cells, BM-MSCs)和脂肪干细胞(ASCs)治疗心肌梗塞已表现出大有希望的结果.已证实移植间充质干细胞治疗心肌梗塞能够改善模式动物的左心室功能.在这项研究中,我们比较了一名患有冠状动脉粥样硬化的老年人捐献的ASCs和BMSCs随机地被移植到两组心肌梗塞模式大鼠体内且这些大鼠不需服用免疫抑制药物时的疗效."

研究人员注意到细胞供者的年龄和健康是重要的因子,还注意到利用来自患有心肌缺血的老年病人的细胞进行细胞移植的影响需要被阐释.

研究人员发现在接受ASCs移植的一组大鼠中,ASCs缓解心肌梗塞发作后的心力衰竭,而接受BMSCs移植的一组大鼠没有表现出类似的益处.他们发现BMSCs要比ASCs分泌出显著更大数量的血管内皮生长因子(vascular endothelial growth factor, VEGF),但是并不产生更好的血管新生反应.此外,接受ASCs移植的一组大鼠在左心室功能上发生改善.

研究人员说,这两种类型的干细胞并不诱导心肌血管新生也让人们对供者年龄和健康是否影响用于治疗心肌梗塞的干细胞疗效产生怀疑.

他们作出结论,"尽管这项研究支持之前的发现：当与BMSCs相比时,ASCs更不可能因衰老而在数量和疗效上下降,但是人们还需要确定来自患有冠状动脉粥样硬化的老年病人的间充质干细胞的特征."

与心肌梗塞相关的拓展阅读：

• Lancet：遗传引起的血浆HDL胆固醇升高与心肌梗塞风险无关
• Nature:心肌梗塞加重动脉粥样硬化进展
• JBC：脂肪细胞分泌的一种激素或可缓解心肌梗塞
• JAMA：心肌梗塞后血钾浓度与住院死亡率相关
• Lancet：心脏干细胞疗法治疗心肌梗塞临床试验获成效
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DOI:10.3727/096368912X659871
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Comparison Of Human Adipose-Derived Stem Cells And Bone Marrow-Derived Stem Cells In A Myocardial Infarction Model

Jeppe Grndahl Rasmussen, Ole Frbert, Claus Holst-Hansen, Jens Kastrup, Ulrik Baandrup, Vladimir Zachar, Trine Fink, Ulf Simonsen

Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully grown non-immunecompromised rat model. Methods: Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were randomised to receive intramyocardial injections of adipose-derived stem cells, bone marrow derived mesenchymal stem cells or phosphate-buffered saline one week following induction of myocardial infarction. Results: After four weeks, left ventricular ejection fraction was improved in the adipose-derived stem cell group and scar wall thickness was greater compared with the saline group. Adipose-derived as well as bone marrow-derived mesenchymal stem cells prevented left ventricular end diastolic dilatation. Neither of the cell groups displayed increased angiogenesis in the myocardium compared with the saline group.Conclusions: Adipose-derived stem cells from a human ischemic patient preserved cardiac function following myocardial infarction whereas this could not be demonstrated for bone marrow-derived mesenchymal stem cells, with only adipose-derived stem cells leading to an improvement in left ventricular ejection fraction. Neither of the stem cell types induced myocardial angiogenesis raising the question whether donor age and health have an effect on the efficacy of stem cells used in the treatment of myocardial infarction.