Mesenchymal stem cells for cardiac therapy: practical challenges and potential mechanisms.
Mesenchymal stem cells for cardiac therapy: practical challenges and potential mechanisms.
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DOI：
10.1007/s12015-012-9375-6
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发表时间：
2013-06
影响因子：
4.8
通讯作者：
Costa KD
中科院分区：
文献类型：
--
作者：
Cashman TJ;Gouon-Evans V;Costa KD
基于细胞的心肌梗死治疗已经在实验室和I期临床试验中证明了疗效，但对这种疗法的理解仍然不完整。间充质干细胞（MSC）被经典地定义为维持产生间充质来源的细胞类型（即脂肪细胞、软骨细胞和骨细胞）的能力。最近的证据表明，这些细胞实际上可能具有比最初认识到的更大的潜力，因为几个研究小组已经发现MSC可以在体外形成心脏谱系细胞。此外，实验性的骨髓间充质干细胞与心肌细胞的共培养似乎可以改善后者的收缩功能。在这些发现的支持下，一些临床试验已经开始测试MSC移植用于改善人类患者的梗死后心脏功能。这些试验的结果喜忧参半，强调需要对干细胞生物学的基础进行更深入的了解。为了帮助综合关于该主题的研究广度，本文讨论了MSC细胞疗法用于心脏修复领域目前面临的挑战，包括细胞递送方法和分子标记物的鉴定，这些分子标记物可以准确地指定治疗相关的间充质细胞类型。MSC介导的心脏改善的各种可能的机制，包括体细胞重编程，转分化，旁分泌信号，和直接电生理耦合也进行了审查。最后，我们考虑了传统的细胞培养微环境，以及心脏组织工程提供仿生体外模型系统的承诺，以更忠实地研究MSC生物学，帮助安全有效地将实验室中令人兴奋的发现转化为临床上有意义的疗法。
Cell based treatments for myocardial infarction have demonstrated efficacy in the laboratory and in phase I clinical trials, but the understanding of such therapies remains incomplete. Mesenchymal stem cells (MSCs) are classically defined as maintaining the ability to generate mesenchyme-derived cell types, namely adipocytes, chondrocytes and osteocytes. Recent evidence suggests these cells may in fact harbor much greater potency than originally realized, as several groups have found that MSCs can form cardiac lineage cells in vitro. Additionally, experimental coculture of MSCs with cardiomyocytes appears to improve contractile function of the latter. Bolstered by such findings, several clinical trials have begun to test MSC transplantation for improving post-infarct cardiac function in human patients. The results of these trials have been mixed, underscoring the need to develop a deeper understanding of the underlying stem cell biology. To help synthesize the breadth of studies on the topic, this paper discusses current challenges in the field of MSC cellular therapies for cardiac repair, including methods of cell delivery and the identification of molecular markers that accurately specify the therapeutically relevant mesenchymal cell types. The various possible mechanisms of MSC mediated cardiac improvement, including somatic reprogramming, transdifferentiation, paracrine signaling, and direct electrophysiological coupling are also reviewed. Finally, we consider the traditional cell culture microenvironment, and the promise of cardiac tissue engineering to provide biomimetic in vitro model systems to more faithfully investigate MSC biology, helping to safely and effectively translate exciting discoveries in the laboratory to meaningful therapies in the clinic.
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影响因子：
24
作者：
Hare, Joshua M.;Traverse, Jay H.;Henry, Timothy D.;Dib, Nabil;Strumpf, Robert K.;Schulman, Steven P.;Gerstenblith, Gary;DeMaria, Anthony N.;Denktas, Ali E.;Gammon, Roger S.;Hermiller, James B., Jr.;Reisman, Mark A.;Schaer, Gary L.;Sherman, Warren
通讯作者：
Sherman, Warren
DOI：
10.1126/science.1177350
发表时间：
2009-10-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Domian IJ;Chiravuri M;van der Meer P;Feinberg AW;Shi X;Shao Y;Wu SM;Parker KK;Chien KR
通讯作者：
Chien KR
影响因子：
20.1
作者：
Hatzistergos KE;Quevedo H;Oskouei BN;Hu Q;Feigenbaum GS;Margitich IS;Mazhari R;Boyle AJ;Zambrano JP;Rodriguez JE;Dulce R;Pattany PM;Valdes D;Revilla C;Heldman AW;McNiece I;Hare JM
通讯作者：
Hare JM
影响因子：
37.8
作者：
Chang, MG;Tung, L;Abraham, R
通讯作者：
Abraham, R
DOI：
10.1152/ajpheart.01087.2009
发表时间：
2010-05-01
影响因子：
4.8
作者：
Abarbanell, Aaron M.;Wang, Yue;Meldrum, Daniel R.
通讯作者：
Meldrum, Daniel R.