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Cardiac stem cells generate new cardiac myocytes during normal cardiac development and pathological hypertrophy.

机译:在正常心脏发育和病理性肥大过程中,心脏干细胞会产生新的心肌细胞。

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摘要

The heart has historically been regarded as a post-mitotic organ incapable of cellular renewal. Recent studies suggest that the adult heart maintains the capacity to generate new myocytes from cardiac stem cells. This study sought to determine if a cell population capable of differentiating into cardiac myocytes was present in the feline heart, if new myocyte formation was part of normal adolescent growth in the feline myocardium, and if the newly formed myocytes had functionally distinct calcium handling and contractile properties. We further examined if newly formed myocytes contributed to the pathological growth of the heart induced by hemodynamic stress, and if those newly formed myocytes exhibited a dysfunctional phenotype.;We identified a population of immature cells in the healthy adolescent feline heart that expressed the stem cell marker c-kit and differentiated into endothelial cells, smooth muscle cells, and cardiac myocytes in vitro. We found that new myocyte formation contributes significantly to the adolescent growth of the feline heart; that the adolescent heart has a population of small mononucleated ventricular myocytes that show evidence of cell cycle activity and proliferative potential; and that these new myocytes have physiological properties reminiscent of fetal or neonatal myocytes.;In the pressure overloaded heart, we found that the increase in heart size is significantly greater than the increase in myocyte volume; that evidence of cell cycle activity is higher in small, mononucleated myocytes than in large, binucleated myocytes; that the ratio of mono- to binucleated myocytes does not change; and that the small, mononucleated myocytes have contractile properties similar to binucleated myocytes from the stressed hearts. These data support our hypothesis that myocyte hyperplasia contributes significantly to cardiac growth in response to pressure overload.;This endogenous growth and repair mechanism in the young heart offers optimism for therapeutic application in heart failure.
机译:历史上,心脏一直被认为是无法进行细胞更新的有丝分裂后器官。最近的研究表明,成年心脏保持了从心脏干细胞产生新的心肌细胞的能力。这项研究试图确定猫的心脏中是否存在能够分化为心肌细胞的细胞群,新的心肌细胞的形成是否是猫心肌正常青春期生长的一部分,以及新形成的心肌细胞在功能上是否具有独特的钙处理能力和收缩能力。属性。我们进一步检查了新形成的心肌细胞是否对由血流动力学压力诱导的心脏病理生长做出了贡献,以及这些新形成的心肌细胞是否表现出功能异常的表型。我们在健康的青春期猫心脏中鉴定了表达干细胞的未成熟细胞群体。标记c-kit,并在体外分化为内皮细胞,平滑肌细胞和心肌细胞。我们发现新的心肌细胞形成对猫心脏的青春期生长有显着贡献。青春期心脏中有一群小的单核心室心肌细胞,这些细胞显示出细胞周期活动和增殖潜能的证据;在压力超负荷的心脏中,我们发现心脏大小的增加明显大于心肌细胞体积的增加。在小的单核肌细胞中,细胞周期活动的证据要比在大的双核肌细胞中更高;单核和双核肌细胞的比例不变;以及小而单核的心肌细胞的收缩特性类似于受压心脏中的双核心肌细胞。这些数据支持了我们的假设,即心肌细胞增生在压力超负荷时对心脏的生长有显着贡献。这种幼年心脏的内源性生长和修复机制为心力衰竭的治疗应用提供了乐观。

著录项

  • 作者

    Wilson, Rachel.;

  • 作者单位

    Temple University.;

  • 授予单位 Temple University.;
  • 学科 Biology Cell.;Biology Physiology.
  • 学位 Ph.D.
  • 年度 2008
  • 页码 106 p.
  • 总页数 106
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

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