Myocardial interstitial fluid inhibits proliferation and cardiomyocyte differentiation in pluripotent embryonic stem cells.
Myocardial interstitial fluid inhibits proliferation and cardiomyocyte differentiation in pluripotent embryonic stem cells.
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心肌间质液抑制多能胚胎干细胞的增殖和心肌细胞分化。
DOI：
10.1152/ajpheart.00172.2009
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Lough,John
中科院分区：
文献类型：
--
作者：
VanOrman,JordanR;Weihrauch,Dorothee;Warltier,DavidC;Lough,John
近年来的研究表明，多能性小鼠胚胎干细胞（mESCs）移植可以改善或恢复梗死心肌的功能。虽然肌再生的程度及其对功能恢复的作用尚不清楚，但这些结果可能受到梗死和/或缺血环境因素的强烈影响。作为了解宿主心肌缺血环境如何影响移植多能细胞的第一步，我们采取了一种简化的方法，其中mESC在含有缺血性心肌间质液（iMIF）的培养基中培养。iMIF在8小时短暂缺血发作期间在犬心肌中产生，并在24天的收集期内每天收集。iMIF在培养11天后强烈减少多能mESC的数量。这种抑制作用是由细胞增殖抑制引起的，对于24天采集期早期时间点的iMIF合并液最为明显。iMIF还抑制多能mESC分化为心肌细胞。相比之下，血管平滑肌和内皮细胞标志物的表达相对不受影响，这与iMIF促进血管生成的先前发现一致。总之，这些结果表明，而缺血/梗死的环境是有利于干细胞介导的血管生成，它是敌对的心肌发生。这些发现还意味着，多能细胞移植后mESC介导的心脏功能改善的观察结果并不反映肌肉化。
Several recent studies have demonstrated that the transplantation of pluripotent murine embryonic stem cells (mESCs) can improve or restore the function of infarcted myocardium. Although the extent of remuscularization and its contribution to the restoration of function are unclear, these outcomes are likely strongly influenced by factors in the infarcted and/or ischemic environment. As an initial step toward understanding how the ischemic environment of host myocardium affects transplanted pluripotent cells, we have taken a reductionist approach wherein mESCs are cultured in medium containing ischemic myocardial interstitial fluid (iMIF). iMIF is generated in canine myocardium during eight hourly episodes of transient ischemia and collected on a daily basis, over a 24-day collection period. iMIF strongly reduced the numbers of pluripotent mESCs after 11 days in culture. This inhibitory effect, which was most pronounced for iMIF pools from early time points of the 24-day collection period, resulted from an inhibition of cell proliferation. iMIF also inhibited the differentiation of pluripotent mESCs into cardiomyocytes. By contrast, the expression of vascular smooth muscle and endothelial cell markers was relatively unaffected, consistent with previous findings that iMIF promotes angiogenesis. Taken together, these results suggest that whereas the ischemic/infarcted environment is favorable to stem cell-mediated angiogenesis, it is hostile to cardiac myogenesis. These findings also imply that observations of mESC-mediated improvement of cardiac function after transplantation of pluripotent cells do not reflect remuscularization.
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冠状动脉侧支期间触珠蛋白的表达和活性。
DOI：
10.1152/ajpheart.00938.2004
发表时间：
2005
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Lohr,NicoleL;Warltier,DavidC;Chilian,WilliamM;Weihrauch,Dorothee
通讯作者：
Weihrauch,Dorothee
大鼠α心肌肌球蛋白重链基因表达的转录后调节。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Sindhwani,R;Ismail-Beigi,F;Leinwand,LA
通讯作者：
Leinwand,LA
DOI：
10.1152/ajpheart.00621.2002
发表时间：
2003-07-01
影响因子：
4.8
作者：
Matsunaga, T;Warltier, DC;Chilian, WM
通讯作者：
Chilian, WM
影响因子：
56.9
作者：
Yu, Junying;Vodyanik, Maxim A.;Thomson, James A.
通讯作者：
Thomson, James A.
DOI：
10.1152/ajpheart.01247.2003
发表时间：
2004-08-01
影响因子：
4.8
作者：
Hodgson, DM;Behfar, A;Terzic, A
通讯作者：
Terzic, A