Shiba Yuji, Hauch Kip D, Laflamme Michael A
Department of Pathology, University of Washington, Seattle, WA 98109, USA.
Curr Pharm Des. 2009;15(24):2791-806. doi: 10.2174/138161209788923804.
Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can self-renew indefinitely, while maintaining the capacity to differentiate into useful somatic cell types, including cardiomyocytes. As such, these stem cell types represent an essentially inexhaustible source of committed human cardiomyocytes of potential use in cell-based cardiac therapies, high-throughput screening and safety testing of new drugs, and modeling human heart development. These stem cell-derived cardiomyocytes have an unambiguous cardiac phenotype and proliferate robustly both in vitro and in vivo. Recent transplantation studies in preclinical models have provided exciting proof-of-principle for their use in infarct repair and in the formation of a "biological pacemaker". While these successes give reason for cautious optimism, major challenges remain to the successful application of hESCs (or hiPSCs) to cardiac repair, including the need for preparations of high cardiac purity, improved methods of delivery, and approaches to overcome immune rejection and other causes of graft cell death. In this review, we describe the phenotype of hESC- and hiPSC-derived cardiomyocytes, the state of preclinical transplantation studies with these cells, and potential approaches to overcome the aforementioned hurdles.
人类胚胎干细胞（hESCs）和诱导多能干细胞（hiPSCs）能够无限自我更新，同时保持分化为有用的体细胞类型的能力，包括心肌细胞。因此，这些干细胞类型代表了一种基本上取之不尽的人类定向心肌细胞来源，可用于基于细胞的心脏治疗、新药的高通量筛选和安全性测试，以及模拟人类心脏发育。这些干细胞衍生的心肌细胞具有明确的心脏表型，并且在体外和体内都能强劲增殖。最近在临床前模型中的移植研究为它们用于梗死修复和“生物起搏器”的形成提供了令人兴奋的原理证明。虽然这些成功带来了谨慎乐观的理由，但将hESCs（或hiPSCs）成功应用于心脏修复仍面临重大挑战，包括需要制备高心脏纯度的细胞、改进的递送方法，以及克服免疫排斥和其他导致移植细胞死亡原因的方法。在这篇综述中，我们描述了hESC和hiPSC衍生的心肌细胞的表型、使用这些细胞进行临床前移植研究的现状，以及克服上述障碍的潜在方法。
