Derivation of a cardiopoietic population from human mesenchymal stem cells yields cardiac progeny.
Derivation of a cardiopoietic population from human mesenchymal stem cells yields cardiac progeny.
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DOI：
10.1038/ncpcardio0429
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发表时间：
2006-03-01
影响因子：
--
通讯作者：
Terzic, Andre
中科院分区：
文献类型：
--
作者：
Behfar, Atta;Terzic, Andre
干细胞已经成为治疗心血管疾病的下一代疗法。在心肌梗死患者中进行的初步临床试验证明，在注射干细胞后，心脏功能得到改善，将干细胞的再生潜力从长凳转移到床边。然而，基于干细胞的治疗的前景尚未得到充分开发，部分原因是对后续治疗的疗效不同。导致这一不确定结果的原因是患者来源的干细胞具有不同的生心潜能。这里制定了一种模拟心脏信号的策略，将来自人骨髓的间充质干细胞转化为心脏祖细胞。我们鉴定了一组重组营养因子，它们能够共同诱导心脏特异转录因子的核移位，使间充质干细胞参与心脏的生成，最终获得具有功能性兴奋-收缩偶联的表型。最大化人骨髓间充质干细胞的生心潜能是优化治疗性翻译的关键一步。
Stem cells have emerged as a next-generation therapy for cardiovascular disease. Initial clinical trials in patients with myocardial infarction document improved cardiac performance after administration of stem cells, translating their regenerative potential from the bench to the bedside. However, the promise of stem cell-based therapy has yet to be fully exploited, in part due to varying degrees of efficacy on follow-up. Contributing to the uncertain outcome is the variable cardiogenic potential of patient-derived stem cells. A strategy mimicking cardiogenic signaling was here formulated to transform mesenchymal stem cells, derived from human bone marrow, into cardiac progenitors. We identified a set of recombinant trophic factors capable of collectively inducing nuclear translocation of cardiac-specific transcription factors, engaging mesenchymal stem cells into cardiopoiesis, and ultimately securing a phenotype with functional excitation-contraction coupling. Maximizing the cardiogenic potential of human mesenchymal stem cells achieves a critical step in optimizing therapeutic translation.