Cardiospheres recapitulate a niche-like microenvironment rich in stemness and cell-matrix interactions, rationalizing their enhanced functional potency for myocardial repair.
Cardiospheres recapitulate a niche-like microenvironment rich in stemness and cell-matrix interactions, rationalizing their enhanced functional potency for myocardial repair.
复制标题
DOI：
10.1002/stem.532
复制
发表时间：
2010-11
期刊：
影响因子：
5.2
通讯作者：
Marban, Eduardo
中科院分区：
文献类型：
--
作者：
Li, Tao-Sheng;Cheng, Ke;Lee, Shuo-Tsan;Matsushita, Satoshi;Davis, Darryl;Malliaras, Konstantinos;Zhang, Yiqiang;Matsushita, Noriko;Smith, Rachel Ruckdeschel;Marban, Eduardo
心脏干细胞是用于心肌再生治疗的有希望的候选者。我们测试的假设是，生长心脏来源的细胞作为三维心脏球可能重演干细胞龛样微环境，有利于细胞存活和增强移植到受伤的心脏后的功能效益。将来自人肌内膜活检的心脏干细胞和支持细胞作为心脏球生长，并与传统单层条件下培养的细胞或从心脏球中分离的细胞进行比较。在悬浮培养中，微球在体外自组装成干细胞龛样结构，同时表现出更大比例的c-kit+细胞和上调的SOX 2和Nanog表达。pathway focused PCR array、定量RT-PCR和免疫组化显示，心肌细胞中干细胞相关因子和粘附/细胞外基质分子（ECM）表达增强，包括IGF-1、HDAC 2、Tert、整合素-α2、层粘连蛋白-β1和MMPs。相对于单层培养的细胞，在患有急性梗死的SCID小鼠心脏中植入心脏微球不成比例地改善了细胞植入和心肌功能。心脏球解离成单细胞会降低细胞外基质和粘附分子的表达，并破坏对氧化应激的抵抗力，从而抵消体内细胞移植和功能益处的改善。作为心脏球的心脏衍生细胞的生长模拟干细胞小生境特性，具有增强的“干性”以及ECM和粘附分子的表达。这些变化是植入梗死心脏后细胞存活率增加和整体功能更有效增强的基础。
Cardiac stem cells are promising candidates for use in myocardial regenerative therapy. We test the hypothesis that growing cardiac-derived cells as three-dimensional cardiospheres may recapitulate a stem cell niche-like microenvironment, favoring cell survival and enhancing functional benefit after transplantation into the injured heart. Cardiac stem cells and supporting cells from human endomyocardial biopsies were grown as cardiospheres and compared to cells cultured under traditional monolayer condition or dissociated from cardiospheres. Cardiospheres self-assembled into stem cell niche-like structures in vitro in suspension culture, while exhibiting greater proportions of c-kit+ cells and up-regulated expression of SOX2 and Nanog. Pathway-focused PCR array, quantitative RT-PCR, and immunostaining revealed enhanced expression of stem cell-relevant factors and adhesion/extracellular-matrix molecules (ECM) in cardiospheres, including IGF-1, HDAC2, Tert, integrin-α2, laminin-β1 and MMPs. Implantation of cardiospheres in SCID mouse hearts with acute infarction disproportionately improved cell engraftment and myocardial function, relative to monolayer-cultured cells. Dissociation of cardiospheres into single cells decreased the expression of ECM and adhesion molecules and undermined resistance to oxidative stress, negating the improved cell engraftment and functional benefit in vivo. Growth of cardiac-derived cells as cardiospheres mimics stem cell niche properties, with enhanced “stemness” and expression of ECM and adhesion molecules. These changes underlie an increase in cell survival and more potent augmentation of global function following implantation into the infarcted heart.
登录
查看更多内容
影响因子：
3.7
作者：
Davis DR;Zhang Y;Smith RR;Cheng K;Terrovitis J;Malliaras K;Li TS;White A;Makkar R;Marbán E
通讯作者：
Marbán E
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
20.1
作者：
Chen, Xiongwen;Wilson, Rachel M.;Houser, Steven R.
通讯作者：
Houser, Steven R.
DOI：
10.1152/ajpheart.00261.2002
发表时间：
2002-08-01
影响因子：
4.8
作者：
Li, TS;Hamano, K;Matsuzaki, M
通讯作者：
Matsuzaki, M
影响因子：
5.2
作者：
Davis, Darryl R.;Smith, Rachel Ruckdeschel;Marban, Eduardo
通讯作者：
Marban, Eduardo