Therapeutic efficacy of human umbilical cord blood-derived mesenchymal stem cells in myocardial repair after infarction

Human UCB-MSCs showed donor-specific variation of therapeutic efficacy in improving LV systolic function, reducing infarct area, and preserving wall thickness after MI, even though there were no significant differences in MSC phenotypes. UCB-MSCs (M02) which showed better efficacy had better paracrine activity and unique gene expression profile than others. In DNA microarray, in contrast to M01, M02 showed unique gene expression profiles; up-regulated anti-apoptotic and down-regulated apoptotic gene expression. To evaluate the correlation of gene expression profile and therapeutic efficacy of UCB-MSCs, we selected two UCB-MSCs (M01 and M02) which showed worst and best efficacy, respectively, in improving post-infarction LV remodeling. Under 3 days differentiation condition as described previously, we compared four groups of UCB-MSCs (naïve M01, differentiated M01, naïve M02 and differentiated M02). And, we examined the transcriptome profiles of undifferentiated and differentiated cells using Affymetrix Human Genome U133 Plus 2.0 Array covering more than 47,000 human transcripts.

人类脐带血间充质干细胞（UCB-MSCs）在心肌梗死（Myocardial Infarction, MI）后改善左心室（Left Ventricle, LV）收缩功能、缩小梗死面积以及维持室壁厚度的治疗效果存在供体特异性差异，尽管不同供体来源的UCB-MSCs的表型并无显著差异。治疗效果更优的UCB-MSCs（M02）相较于其他供体细胞，具备更强的旁分泌活性与独特的基因表达谱。在基因芯片（DNA microarray）检测中，与M01相比，M02呈现出独特的基因表达特征：抗凋亡基因表达上调，而凋亡基因表达下调。为探究UCB-MSCs的基因表达谱与治疗效果之间的相关性，我们选取了在改善梗死后左心室重构方面疗效最差与最优的两株UCB-MSCs，即M01与M02。参照此前报道的3天诱导分化培养方案，我们对四组UCB-MSCs进行了对比分析，分别为未分化M01、分化后M01、未分化M02以及分化后M02。此外，我们采用覆盖超过47000个人类转录本的Affymetrix Human Genome U133 Plus 2.0基因芯片，对未分化与分化后的细胞进行了转录组谱分析。