Transcriptional profiling of young and old mesenchymal stem cells in response to oxygen deprivation and reparability of the infarcted myocardium
Transcriptional profiling of young and old mesenchymal stem cells in response to oxygen deprivation and reparability of the infarcted myocardium
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DOI：
10.1016/j.yjmcc.2007.11.014
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发表时间：
2008-03-01
影响因子：
5
通讯作者：
Ashraf, Muhammad
中科院分区：
文献类型：
--
作者：
Jiang, Shujia;Haider, Husnain Kh;Ashraf, Muhammad
大多数临床研究使用自体骨髓（BM）干细胞进行老年患者心肌再生。我们假设衰老会损害骨髓干细胞的生存和分化潜力，从而限制其治疗效果。从年轻((MSCs)-M-Yng；8-12周)和龄((MSCs)- m龄；对24-26个月大鼠进行纯化，评估其对缺氧的反应和梗死心脏的修复能力。与(MSCs)-M-Yng单独培养或与(MSCs)-M-Yng共培养（Co-oldMSCs）相比，(MSCs)-M-Yng在缺氧条件下血管生成生长因子的表达更高。同样，在体外Matrigel实验中，与(MSCs) -M-old和Co-oldMSCs相比，(MSCs)-M-Yng对凋亡刺激的耐受性更强，形成管状结构的能力更高，p21和p27可能是促进存活的因素。体内实验采用fisher -344大鼠（n=38）建立急性心肌梗死模型。各组分别接受70 μ 1无细胞DMEM（1组）或含有2 × 10(6) (MSCs)-M-Yng （PKH67标记，2组）或(MSCs) -M-old （PKH26标记，3组）和(MSCs)-M-Yng + (MSCs) -M-old （1 × 10(6)个细胞）的混合物；4)。组织学研究显示，到第7天，(MSCs)-M-Yng呈细长形态，取向与宿主肌肉结构相似。电镜和荧光免疫染色后的共聚焦成像显示(MSCs)-M-Yng具有优越的血管生成潜能。超声心动图显示，移植(MSCs)-M-Yng的动物心功能指标明显保留。衰老损害(MSCS)-M-old对缺氧的反应性及其分化潜能。（MSCs）-M-Yng在体内和体外均不能改变(MSCs) -M-old的存活。因此，在未来的临床研究中，年轻供体的干细胞移植将是一个更好的心脏细胞治疗选择。(C) 2007爱思唯尔公司版权所有。
Most clinical studies have used autologous bone marrow (BM) stem cells for myocardial regeneration in elderly patients. We hypothesize that aging impairs the survival and differentiation potential of BM stem cells thus limiting their therapeutic efficacy. BM-derived MSCs from young ((MSCs)-M-Yng; 8-12 weeks) and old ( (MSCs)-M-old; 24-26 months) rats were purified and assessed for their responsiveness to anoxia and reparability of infarcted heart. Higher expression of angiogenic growth factors was observed by (MSCs)-M-Yng under anoxia as compared to (MSCs)-M-old, cultured either alone or in co-culture (Co-oldMSCs) with (MSCs)-M-Yng. Likewise, (MSCs)-M-Yng were more tolerant to apoptotic stimuli and showed higher ability to form tubular structures during in vitro Matrigel assay as compared to (MSCS)-M-old and Co-oldMSCs with a possible role of p21 and p27 as contributory survival factors. For in vivo studies, acute myocardial infarction model was developed in Fischer-344 rats (n=38). The animals were grouped to receive 70 mu 1 basal DMEM without cells (group 1) or containing 2 X 10(6) (MSCs)-M-Yng (PKH67 labeled; group 2) or (MSCS)-M-old (PKH26 labeled; group 3) and mixture of (MSCs)-M-Yng + (MSCS)-M-old (1 X 10(6) cells each; group 4). Histological studies revealed that by day 7, (MSCs)-M-Yng showed elongated morphology with orientation similar to the host muscle architecture. Electron microscopy and confocal imaging after fluorescent immunostaining showed superior angiomyogenic potential of (MSCs)-M-Yng. Echocardiography showed significantly preserved heart function indices in the animals transplanted with (MSCs)-M-Yng. Aging impairs the responsiveness of (MSCS)-M-old to anoxia and their differentiation potential. (MSCs)-M-Yng fail to alter the survival of (MSCS)-M-old under in vitro as well as in vivo conditions. It is therefore concluded that transplantation of stem cells from young donors would be a better option for heart cell therapy in future clinical studies. (C) 2007 Elsevier Inc. All rights reserved.