Use of mesenchymal stem cells for therapy of cardiac disease.
Use of mesenchymal stem cells for therapy of cardiac disease.
复制标题
使用间充质干细胞治疗心脏病。
DOI：
10.1161/circresaha.116.303614
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发表时间：
2015-04-10
影响因子：
20.1
通讯作者：
Hare JM
中科院分区：
文献类型：
--
作者：
Karantalis V;Hare JM
尽管在过去的65年里，心血管疾病在临床上取得了重大进展，但它仍然是美国人死亡的主要原因。在过去的15年里，人们对干细胞和/或前体细胞作为慢性损伤器官的治疗剂的应用产生了重大的基础和转化兴趣。在所研究的细胞类型中，成体间充质干细胞（MSC）被广泛研究，并且在早期临床研究中显示出用于心脏组织修复和再生的前景。MSC分化成中胚层和非中胚层来源的组织的能力、它们的免疫调节作用、它们的可用性以及它们在维持和补充内源性干细胞小生境中的关键作用使它们成为最深入研究和临床测试的干细胞类型之一。来自临床前和早期临床试验的累积数据证明了它们在一系列心血管疾病中以自体或同种异体形式递送时的安全性，但也重要地定义了临床疗效参数，这些参数证明了在更大的临床试验中进一步研究的合理性。在这里，我们回顾了间充质干细胞的生物学，它们与内源性分子和细胞途径的相互作用，以及它们对免疫反应的调节。此外，我们还讨论了增强其增殖和再生能力的因素以及可能阻碍其在临床环境中有效性的因素。
Despite substantial clinical advances over the past 65 years, cardiovascular disease remains the leading cause of death in America. The past 15 years has witnessed major basic and translational interest in the use of stem and/or precursor cells as a therapeutic agent for chronically injured organs. Among the cell types under investigation, adult mesenchymal stem cells (MSCs) are widely studied and in early stage clinical studies show promise for repair and regeneration of cardiac tissues. The ability of MSCs to differentiate into mesoderm and non-mesoderm derived tissues, their immunomodulatory effects, their availability and their key role in maintaining and replenishing endogenous stem cell niches have rendered them one of the most heavily investigated and clinically tested type of stem cell. Accumulating data from preclinical and early phase clinical trials document their safety when delivered as either autologous or allogeneic forms in a range of cardiovascular diseases, but also importantly define parameters of clinical efficacy that justify further investigation in larger clinical trials. Here, we review the biology of MSCs, their interaction with endogenous molecular and cellular pathways, and their modulation of immune responses. Additionally, we discuss factors that enhance their proliferative and regenerative ability and factors that may hinder their effectiveness in the clinical setting.