Dynamic Support Culture of Murine Skeletal Muscle-Derived Stem Cells Improves Their Cardiogenic Potential In Vitro.
Dynamic Support Culture of Murine Skeletal Muscle-Derived Stem Cells Improves Their Cardiogenic Potential In Vitro.
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DOI：
10.1155/2015/247091
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发表时间：
2015
影响因子：
4.3
通讯作者：
Choi YH
中科院分区：
文献类型：
--
作者：
Neef K;Treskes P;Xu G;Drey F;Srinivasan SP;Saric T;Nembo E;Semmler J;Nguemo F;Stamm C;Cowan DB;Deppe AC;Scherner M;Wittwer T;Hescheler J;Wahlers T;Choi YH
缺血性心脏病是西方国家的主要死亡原因，在全球范围内其负担正在增加。它通常涉及不可逆转的心肌组织变性和丢失，导致不良的预后和致命的结局。具有再生受损心脏组织能力的自体细胞将是细胞治疗方法的理想来源。在这里，我们比较了不同的条件培养方法，以提高小鼠骨骼肌源性干细胞的产量和生心潜能。通过预先培养和应用不同的细胞培养条件，从骨骼肌分离出非贴壁细胞亚群，以支持簇状结构的形成。与静态培养条件相比，无论有无预先悬滴预培养，动态培养均能显著增加心肌簇径，并在蛋白和mRNA水平上表达心脏特异性标志物。全细胞膜片钳研究显示起搏器动作电位和对心脏特定药物刺激的反应性相似。这一数据表明，骨骼肌源性干细胞能够通过应用特定的培养条件来采用增强的心肌细胞样属性。选择这一路线为心脏治疗建立可持续的、自体的细胞来源具有比转基因操作细胞更容易被临床接受的潜力。
Ischemic heart disease is the main cause of death in western countries and its burden is increasing worldwide. It typically involves irreversible degeneration and loss of myocardial tissue leading to poor prognosis and fatal outcome. Autologous cells with the potential to regenerate damaged heart tissue would be an ideal source for cell therapeutic approaches. Here, we compared different methods of conditional culture for increasing the yield and cardiogenic potential of murine skeletal muscle-derived stem cells. A subpopulation of nonadherent cells was isolated from skeletal muscle by preplating and applying cell culture conditions differing in support of cluster formation. In contrast to static culture conditions, dynamic culture with or without previous hanging drop preculture led to significantly increased cluster diameters and the expression of cardiac specific markers on the protein and mRNA level. Whole-cell patch-clamp studies revealed similarities to pacemaker action potentials and responsiveness to cardiac specific pharmacological stimuli. This data indicates that skeletal muscle-derived stem cells are capable of adopting enhanced cardiac muscle cell-like properties by applying specific culture conditions. Choosing this route for the establishment of a sustainable, autologous source of cells for cardiac therapies holds the potential of being clinically more acceptable than transgenic manipulation of cells.